Aim: Detection of clinical and subclinical nonthromboembolic PH in MM patients after thalidomide treatment.

Patients and methods: Eighty-two patients, 46–82 years (median age 61 years), 42 males, were studied. They underwent echocardiographic study at baseline, 1 month thereafter, 6 months later and whenever symptoms indicating deterioration of cardiac function appeared. Echocardiographic signs of PH were especially identified.

Results: Clinical and echocardiographic evaluation revealed four patients (out of 82 patients, 4.87%) with PH. Nonimaging and imaging diagnostic methods excluded thromboembolic PH. Statistical analysis demonstrated significant correlation between structural heart disease and PH (r = 14.078; P = 0.008). No significant correlation between age (r = 0.770; P = 0.724), gender (r = 1.157; P = 0.285), International Staging System (ISS) (r = 0.316; P = 0.716) and PH was found.

Conclusions: Preexisted endothelial dysfunction due to structural cardiac disease enhances the vasoactive substances release causing increased pulmonary vascular resistance. Thalidomide possibly causes a vasodilator and vasoconstriction imbalance, which may cause abnormal pulmonary vascular response interfering to a vicious circle perpetuating PH.

Methods: Previously untreated patients with PBC T2–4a–c N0–3 M0 received one cycle of docetaxel 75 mg/m², adriamycin 50 mg/m² and cyclophosphamide 500 mg/m² administered on day 5 combined with escalating doses of oblimersen as a 24-h continuous infusion on days 1–7 followed by five cycles of combination of docetaxel, adriamycin and cyclophosphamide (TAC) without oblimersen every 3 weeks. Prophylactic antibiotic therapy and granulocyte colony-stimulating factor administration were used in all six cycles. Blood serum samples were taken throughout the treatment period for pharmacokinetic analysis.

Results: Twenty-eight patients were enrolled (median age, 50 years; ductal-invasive histology, 68%; tumorsize 2–5 cm, 61%; grade 3, 43%; hormone receptor negative, 36%; Her2 positive 18%) and received oblimersen in a dose of 3 mg/kg/day (cohort I, nine patients), 5 mg/kg/day (cohort II, nine patients) and 7 mg/kg/day (cohort III, 10 patients) respectively. No dose-limiting toxicity occurred. Following oblimersen combined with TAC, the most severe toxicity was neutropenia [National Cancer Institute—Common Toxicity Criteria (NCI-CTC) grades 1–2/3/4] which developed in 0/0/56% of patients (cohort I), 11/0/56% of patients (cohort II) and 20/20/50% of patients (cohort III). No febrile neutropenia occurred. Most common adverse events (all NCI-CTC grade ≤ 2) were fatigue, nausea, alopecia, headache and flue-like symptoms observed in 78% (cohort I), 89% (cohort II) and 90% (cohort III) of patients. With increasing dose of oblimersen, a higher incidence of grade IV leukopenia and neutropenia was noted. At the MTD of 7 mg/kg/day of oblimersen, serious adverse events occurred in 40% of the patients.

Conclusion: Oblimersen up to a dose of 7 mg/kg/day administered as a 24-h infusion on days 1–7 can be safely administered in combination with standard TAC on day 5 as NST in patients with PBC. The safety and preliminary efficacy warrants further evaluation of oblimersen in combination with every cycle of the TAC regimen in a randomized trial.

Methods: In all, 52 patients with HL receiving bleomycin-based chemotherapy with (n = 23) or without (n = 29) mediastinal radiotherapy were enrolled. Pretreatment pulmonary function tests were carried out. These were repeated at 1 month, 6 months, and 1 year after therapy.

Results: With chemotherapy alone, the median %DLCO declined significantly at 1 month but returned to baseline by 6 months. The median %DLCO did not further decrease with radiotherapy, but remained persistently reduced at 1 year. In patients who received radiotherapy, having >33% of lung volume receive 20 Gy (V20) and a mean lung dose (MLD) of >13 Gy significantly predicted for persistently reduced %DLCO at 6 months (P = 0.035). Smoking significantly predicted for a persistently reduced %DLCO at 1 year (P = 0.036). On multivariable analysis, significant predictors for decline in %DLCO at 1 year were higher baseline %DLCO (P = 0.01), higher MLD (P = 0.02), and a smoking history (P = 0.02).

Conclusions: Several factors contribute to decline in %DLCO in HL patients who received bleomycin-based computed tomography. The identification of threshold radiation dosimetric parameters for reduced lung function may provide guidance in the radiation planning of these patients.

Patients and methods: One hundred and nineteen patients with LAPC, World Health Organization performance status of zero to two were randomly assigned to either the induction CHRT group (60 Gy, 2 Gy/fraction; concomitant 5-fluorouracil infusion, 300 mg/m²/day, days 1–5 for 6 weeks; cisplatin, 20 mg/m²/day, days 1–5 during weeks 1 and 5) or the induction gemcitabine group (GEM: 1000 mg/m² weekly for 7 weeks). Maintenance gemcitabine (1000 mg/m² weekly, 3/4 weeks) was given in both arms until disease progression or toxicity.

Results: Overall survival was shorter in the CHRT than in GEM arm [median survival 8.6 (99% confidence interval 7.1–11.4) and 13 months (8.7–18.1), P = 0.03]. One-year survival was, respectively, 32% and 53%. These results were confirmed in a per-protocol analysis for patients who received 75% or more of the planned dose of radiotherapy. More overall grades 3–4 toxic effects were recorded in the CHRT arm, both during induction (36 versus 22%) and maintenance (32 versus 18%).

Conclusion: This intensive induction schedule of CHRT was more toxic and less effective than gemcitabine alone.

Materials and methods: pAKT, pERK, cSRC, E-cadherin, cMET[pY1003], cMET[pY1230/1234/1235], and cMET[pY1349] immunohistochemistry, cMET FISH analysis, and EGFR-, KRAS-, and cMET mutation analysis were carried out on tumor samples from 51 gefitinib-treated NSCLC patients. Biological parameters and survival end points were compared by univariate and multivariate analyses. cMET expression was also investigated in two additional series of patients. The in vitro antiproliferative activity of gefitinib alone or in combination with hepatocyte growth factor and the cMET antibody DN-30 was assessed in NSCLC cells.

Results: EGFR19 deletion and pAKT expression were significantly associated with response (P < 0.0001) and longer time to progression (TTP) (P = 0.007), respectively. Strong cMET[pY1003] membrane immunoreactivity was expressed in 6% of 149 tumors analyzed and was significantly associated with progressive disease (P = 0.019) and shorter TTP (P = 0.041). In vitro, the DN-30 combination synergistically (CI < 1) enhanced gefitinib-induced growth inhibition in all cMET[pY1003]-expressing cell lines studied.

Conclusions: Activated cMET[pY1003] appears to be a marker of primary gefitinib resistance in NSCLC patients. cMET may be a target in treatment of NSCLC.

Patients and methods: We describe a cohort of seven patients and discuss 94 additional cases from the literature for whom biological parameters were described. Cases with incomplete data were excluded.

Results: Hodgkin's disease (HD) was more common in the 18–59 age group while breast and prostate cancers were prevalent only in the ≥18-year-old patients. The time interval to develop sALL was similar among all age groups but was significantly longer for HD and neuroblastoma primary diagnoses and sALL with complex karyotype. T-cell immunophenotype was more common in the <18 age group. Complete remission was infrequent in the ≥60 age group. The overall survival was poor for all sALL regardless of age, primary diagnoses, cytogenetic subgroups, or immunophenotype. Allogeneic transplantation most probably represents the only chance of cure.

Conclusion: Better identification of prognostic factors to prevent the occurrence of sALL is indicated.

Methods: Single-institution retrospective chart review of patients receiving Sm 153. The effect of Sm 153 on peripheral white blood cell (WBC), platelet counts, and change from baseline was calculated.

Results: The available hematologic data from records of 58 patients receiving 100 treatments with Sm 153 were reviewed. Prior treatment with radiotherapy or chemotherapy had no effect on changes from baseline or median nadir counts for either WBC or platelets when compared with patients not having such prior treatments. Multiple treatments with Sm 153 had no effect on change from baseline in WBC or platelet counts as compared with the initial administration. Median survival following the first dose of Sm 153 was 15 months.

Conclusions: Prior treatment with radiotherapy or chemotherapy did not affect the rates of myelotoxicity. Multiple treatments with samarium Sm 153 lexidronam also had no effect on severity of myelotoxicity with successive courses. Patients with bone predominant metastatic disease may survive for extended periods of time and may safely be treated with multiple modalities of therapy.

Patients and methods: All patients diagnosed with primary metastatic colon cancer from 1990 to 2004 in the registration area of the Eindhoven Cancer Registry were included. Date of diagnosis was divided into four periods (1990–1994, 1995–1999, 2000–2002, and 2003–2004) according to the availability of chemotherapy for metastatic colon cancer. We assessed OS according to chemotherapy use and period.

Results: Of the 1769 patients, 30.6% received chemotherapy. Chemotherapy use over time increased from 24% in 1990–1994 to 55% in 2000–2004 for patients aged <70 years and from 2% to 22% in patients aged 70 years and older. Median survival for patients diagnosed in 1990–1994 was 26 [95% confidence interval (CI) 22–32] weeks, while patients diagnosed in 2003–2004 had a median survival of 39 (95% CI 31–48) weeks. Patients who did not receive chemotherapy had a survival of 22 (95% CI 20–25) weeks, while the survival for patients who did receive chemotherapy was 57 (95% CI 51–65) weeks. OS decreased with increasing age (P < 0.0001). In the multivariate survival analysis, chemotherapy use, increasing age, having multiple comorbid conditions, and having more than one tumour site significantly affect survival, with the strongest effect of chemotherapy use.

Conclusion: Palliative chemotherapy significantly improved OS in unselected patients with metastatic colon cancer.

Patients and methods: This was a phase II monocentric study of 30 patients with advanced or metastatic prostate cancer, 29 had castration-resistant prostate cancer and 23 had received prior chemotherapy. Patients received erlotinib: 150 mg/day, increased to 200 mg at week 4, and continued until progression or unacceptable toxicity. Efficacy was defined as a decrease or stabilization of prostate-specific antigen (PSA) without clinical progression. Clinical benefit was evaluated by Karnofsky performance status and pain intensity, and response was an improvement in one of these parameters without worsening in the other.

Results: Median age was 69 years (range 51–77 years), and median PSA 102 ng/ml (range 3–1213 ng/ml). Dose escalation to 200 mg was possible in 16 (55%) patients. Moderate toxicity was observed. No patient had a decrease in PSA, 14% had stabilization, less than the ≥20% expected. PSA-doubling time, evaluated before and after erlotinib, was increased for 10 patients (P = 0.0058). Clinical benefit was achieved in 40% of patients.

Conclusion: Erlotinib demonstrated an improvement in clinical benefit. Future directions should include evaluating its use in less advanced prostate cancer.

Patients and methods: This study is a retrospective subset analysis of 32 patients with T4 laryngeal carcinoma including LVT4 tumors treated on three consecutive protocols investigating paclitaxel (Taxol), 5-fluorouracil, hydroxyurea, and 1.5-Gy twice daily (BID) radiotherapy (TFHX).

Results: Median follow-up is 43 months. Four-year locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and laryngectomy-free survival (LFS) was 71%, 67%, 53%, and 86%, respectively. Four patients required laryngectomy for recurrent or persistent disease. Of disease-free patients with ≥1 year follow-up, 90% demonstrated normal or understandable speech. None required laryngectomy for complications. Among LVT4 patients, 4-year LRC, DFS, OS, and LFS was 71%, 65%, 56%, and 81%, respectively. Induction chemotherapy improved 4-year LRC (90% versus 46%, P = 0.03) and DFS (84% versus 42%, P = 0.03).

Conclusions: Promising control and functional outcomes are achieved with TFHX for T4 laryngeal patients. LVT4 disease had outcomes similar to patients with less advanced disease treated on Radiation Therapy Oncology Group 91-11. Induction chemotherapy improved outcomes, warranting further investigation.

Patients and methods: Twenty-four patients with GTN received TP/TE. Sixteen had failed previous chemotherapy including six with cisplatin-based regimens (group A) and eight changed to TP/TE because of prior treatment-induced toxic effects (group B).

Results: In group A, three patients (19%) achieved a complete response (CR) and five (31%) a partial response (PR). All CR and four PR patients remain alive with a median follow-up of 25 months (range 9–48). The eight patients failing TP/TE subsequently died. Thus, the overall survival of the 16 patients in group A was 44% (seven of 16), rising to 70% (seven of 10) if the six patients who had failed prior cisplatin-based chemotherapy were excluded. In group B, four patients were assessable for response (two CR, two PR) and six remain alive (median follow-up 19 months) giving an overall survival of 75%. TP/TE was well tolerated, with only one patient discontinuing therapy because of toxic effects.

Conclusion: TP/TE is an effective, well-tolerated, salvage treatment for relapsed patients who are heavily pretreated for GTN. Further studies of this regimen are warranted.

Patients and methods: Ten patients, all with World Health Organization grades III–IV oral mucositis in cycles A1/B1, obtained palifermin with subsequent similar or identical cycles to reduce mucositis. Thus, patients serve as their own control for efficacy of palifermin.

Results: All 10 patients developed grades III–IV mucositis in cycles A1/B1 without palifermin, whereas only two of 10 developed grades III–IV mucositis in corresponding cycles A2/B2 with palifermin. Only four of 10 patients showed infections in the cycles with palifermin compared with 10 of 10 patients without palifermin. The duration of mucositits in patients who acquired a higher grade mucositis despite treatment with palifermin could be reduced from 12.9 days (median) without to 11 days with palifermin. The amount of i.v. opioid analgetics could be significantly reduced.

Conclusion: Palifermin might reduce the incidence, severeness and duration of oral mucositis in HD-MTX-based chemotherapy and may influence clinical sequelae such as infection and quality of life.

Patients and methods: The hypothesis was that FDG–PET would improve the negative predictive value (NPV) from 70% to 90%, thus requiring a total of 169 patients. All scans underwent visual analysis by a reference team of nuclear medicine physicians. Results were validated by histology following retroperitoneal lymph node dissection.

Results: Only 72 of the planned 169 patients were included, due to poor accrual. The prevalence of nodal involvement was 26%. Correct nodal staging by FDG–PET was achieved in 83% compared with correct computed tomography (CT) staging in 71%. CT had a sensitivity and specificity of 41% and 95%, respectively. Positive predictive value (PPV) and NPV were 87% and 67%, respectively. FDG–PET had a sensitivity and specificity of 66% and 98%, respectively. PPV was 95%. The primary end point was not reached, with an NPV of 78%.

Conclusion: FDG–PET as a primary staging tool for NSGCT yielded only slightly better results than CT. Both methods had a high specificity while false-negative findings were more frequent with CT. FDG–PET is mostly useful as a diagnostic tool in case of questionable CT scan.

Methods: Systematic review of pertinent information from published literature and meeting abstracts through December 2007 was carried out to identify factors contributing to fracture risk in women with breast cancer. An evidence-based medicine approach was used to select risk factors that can be used to determine when to initiate bisphosphonate treatment of aromatase inhibitor-associated bone loss (AIBL).

Results: Fracture risk factors were chosen from large, well-designed, controlled, population-based trials in postmenopausal women. Evidence from multiple prospective clinical trials in women with breast cancer was used to validate AI therapy as a fracture risk factor. Overall, eight fracture risk factors were validated in women with breast cancer: AI therapy, T-score <–1.5, age >65 years, low body mass index (BMI <20 kg/m²), family history of hip fracture, personal history of fragility fracture after age 50, oral corticosteroid use >6 months, and smoking. Treatment recommendations were derived from randomized clinical trials.

Conclusions: The authors recommend the following for preventing and treating AIBL in women with breast cancer. All patients initiating AI therapy should receive calcium and vitamin D supplements. Any patient initiating or receiving AI therapy with a T-score ≥–2.0 and no additional risk factors should be monitored every 1–2 years for change in risk status and bone mineral density (BMD). Any patient initiating or receiving AI therapy with a T-score <–2.0 should receive bisphosphonate therapy. Any patient initiating or receiving AI therapy with any two of the following risk factors—T-score <–1.5, age >65 years, low BMI (<20 kg/m²), family history of hip fracture, personal history of fragility fracture after age 50, oral corticosteroid use >6 months, and smoking—should receive bisphosphonate therapy. BMD should be monitored every 2 years, and treatment should continue for at least 2 years and possibly for as long as AI therapy is continued. To date, the overwhelming majority of clinical evidence supports zoledronic acid 4 mg every 6 months to prevent bone loss in women at high risk. Although there is a trend towards fewer fractures with zoledronic acid, studies completed to date have not been designed to capture significant differences in fracture rate, and longer follow-up is needed.

Patients and methods: Patients received docetaxel 36 mg/m² i.v. on days 1, 8, and 15 and capecitabine orally 625 mg/m² b.i.d. from days 8 to 21. Cycles were repeated every 4 weeks. In the correlative study, we evaluated the TP expression by immunohistochemistry and the TP messenger RNA expression by real-time RT–PCR in the primary tumor.

Results: Forty-seven women were enrolled. In the intention-to-treat analysis, objective responses were achieved in 24 patients (51%). Fourteen additional patients (30%) had stable disease. The median time to progression (TTP) was 6 months (range 1–44 months). Median survival was 17 months (range 1–48 months). Overall, the treatment was well tolerated. The most common clinical adverse events (all grades) were alopecia (55%), nail changes (53%), fatigue/asthenia (51%), nausea/vomiting (51%), neutropenia (49%), and neuropathy (49%). A significantly higher TTP was observed in patients with TP-positive tumors (log-rank test, P = 0.009). Interestingly, a subgroup analysis confirmed this TTP benefit in patients with TP-positive tumors obtaining a tumor response (log-rank test, P = 0.03), whereas the statistical significance was lost in nonresponders (log-rank test, P = 0.3).

Conclusions: This study indicates that a regimen with low doses of capecitabine plus weekly docetaxel is active against MBC. The correlative analysis provides preliminary evidence that TP expression may be a predictive marker for therapeutic benefit.

Patients and methods: Cetuximab was administered weekly: 400 mg/m² initial dose, then 250 mg/m² and FUFOX: oxaliplatin 50 mg/m², FA 500 mg/m² and 5-FU as a 24-h infusion at either 1500 or 2000 mg/m² administered for 4 weeks followed by a 1-week rest (one cycle).

Results: Dose-limiting toxicity (grade 3 diarrhea) occurred in 3 of 14 assessable patients receiving 5-FU at standard 2000 mg/m². This dose was administered to a further 25 patients. Cetuximab combined with FUFOX was generally well tolerated with the most common grade 3/4 adverse events being diarrhea (27%) and paresthesia (16%). The confirmed response rate for patients receiving 5-FU at standard 2000 mg/m² (N = 41) was 56%, with a median duration of 9.3 months. Median progression-free and overall survival times including all 49 patients were 8.1 (95% confidence interval 6.0–9.7) and 28.2 months, respectively. Cetuximab pharmacokinetics seemed not to be different for combination with FUFOX compared with cetuximab/irinotecan combinations.

Conclusion: This protocol is well tolerated and shows promising efficacy supporting further investigation.

Patients and methods: XRP6258 was administered as a 1-h i.v. infusion every 3 weeks at 20 mg/m² (then, in the absence of severe toxicity, at 25 mg/m² from cycle 2). The primary end point was the objective response rate (ORR) assessed according to response evaluation criteria in solid tumours (RECIST) guidelines.

Results: Seventy-one patients were enrolled. The median relative dose intensity was 0.98. The ORR was 14% (two complete, eight partial responses). Eighteen patients (25%) had stable disease of >3 months duration. At a median follow-up of 20.0 months, the median time to progression was 2.7 months, and the median overall survival 12.3 months. The most common grade 3/4 adverse events (AEs) were neutropenia (73%) and leucopenia (55%), with a low febrile neutropenia rate (3%) and infrequent grade 3/4, treatment-related, non-hematological AEs (<5% patients for any AE). Two deaths were reported, one related to study drug and one to unknown cause.

Conclusions: XRP6258 was active and well tolerated in this group of MBC patients with taxane-resistant disease. These results support the further clinical development of this agent.

Patients and methods: Patients receiving sunitinib at Stanford University from 1 July 2004 to 1 July 2007 were identified. Medical records were reviewed and those patients experiencing symptomatic grade 3/4 left ventricular systolic dysfunction were identified. Potential cardiac risk factors were analyzed.

Results: Forty-eight patients treated with sunitinib were assessable. Seven patients experienced symptomatic grade 3/4 left ventricular dysfunction 22–435 days after initiation of sunitinib. Three patients had persistent cardiac dysfunction after discontinuation of sunitinib and initiation of heart failure therapy. A history of congestive heart failure, coronary artery disease and lower body mass index were factors associated with increased risk.

Conclusions: Among patients treated with sunitinib at our institution, 15% developed symptomatic grade 3/4 heart failure. Future studies of sunitinib-related cardiotoxicity are urgently needed, particularly as the oncologic indications for this drug continue to expand.

Materials and methods: Nude mice bearing A2780s and A2780cp ovarian tumors were treated twice weekly with i.v. administration of 50 µg VSVMP/250 µg liposome complex, 50 µg empty plasmid/250 µg liposome complex, 0.9% NaCl solution or weekly with i.p. administration of cisplatin (5 mg/kg) for 3 weeks. Tumor volume and survival time were observed. TUNEL assay and CD34 vessel staining were conducted in tumor tissue. Antiangiogenesis in vivo were determined by sponge assay. Antiproliferative and apoptosis-inducing activities of VSVMP in vitro were tested on MS1murine endothelial cells and four human ovarian cancer cell lines: A2780s, A2780cp, HO8910 and COC1.

Results: Administration of VSVMP resulted in significant inhibition (87%–98% maximum inhibition relative to controls) in the growth of A2780s and A2780cp tumor xenografts, and prolonged the survival of the treated mice. Complete tumor regression happened in VSVMP-treated mice in both tumor models. These antitumor responses were associated with marked increases in tumor apoptosis and reductions in intratumoral microvessel density.

Conclusions: Our data indicate that VSVMP may provide an effective approach to inhibit both cisplatin-sensitive and -resistant human ovarian cancer growth with minimal side-effects.

Patients and methods: We carried out a tissue microarray that included 80 primary breast tumors obtained before the administration of endocrine therapy. A second tissue microarray included 52 tumors obtained after endocrine therapy from the same patients. Immunostainings were carried out for ER, Pser118ER, Her2, insulin growth factor receptor (IGFR), p21-activated kinase 1 (PAK1), pMAPK, bcl2 and progesterone receptor.

Results: Pser118ER staining was higher in Her2- (P = 0.06), IGFR- (P = 0.0002) and pMAPK-expressing tumors (P = 0.001). The level of ER phosphorylation was not different according to the occurrence of clinical tumor response (P = 0.16). Pser118ER expression was significantly reduced by endocrine therapy. The mean Pser118ER score was 163 [standard deviation (SD) 81] before endocrine therapy and 80 (SD 90) after endocrine therapy (P = 0.0001, paired t-test). The magnitude of Pser118ER decrease was higher in tumors that responded to endocrine therapy (mean decrease 128, SD 86) as compared with refractory tumors (mean decrease 38, SD 130) (P = 0.017, t-test).

Conclusion: These findings suggest that endocrine therapy modulates ER on ser118. Pser118ER immunostaining could be used as surrogate marker to monitor treatment efficacy.

Patients and methods: Patients with T3, T4, N1, N2, N3 or M1 cisplatin advanced penile cancer were treated with a combination of irinotecan (60 mg/m²) on days 1, 8 and 15 and cisplatin (80mg/m²) administered every 28 days. Patients were treated either in the neo-adjuvant setting for T3 or N1–N2 disease with a maximum of four cycles before surgery or up to eight cycles for T4 or N3 or M1 disease. The study was designed with the aim to exclude a response rate (complete response + partial response) <30% ( = 10%, power = 95%).

Results: Twenty-eight patients were included and evaluated for toxicity, and 26 eligible patients were evaluated for response. Toxicity was acceptable with three cases of grade 3 diarrhoea and two cases of grade 4 neutropenic fever. There were eight responses (two complete response and six partial response) (30.8%, 80% confidence interval 18.8% to 45.1%): three patients undergoing histological verification after chemotherapy had no evidence of malignancy.

Conclusion: The study fails to demonstrate a response rate significantly >30%.The observation regarding M0 patients suggests to repeat this study in the neo-adjuvant setting.

Patients and methods: FCGR3B-NA1/NA2 genotypes were determined in 46 patients having received rituximab for a previously untreated, follicular, non-Hodgkin's lymphoma. The clinical response and the disappearance of the BCL2-JH gene rearrangement in both peripheral blood and bone marrow were evaluated at 2 months (M2) and each year during 7 years.

Results: They were 13% homozygous for FCGR3B-NA1, 61% homozygous for FCGR3B-NA1/NA2 and 26% heterozygous. The objective response rates at M2 were 67% in homozygous FCGR3B-NA1 patients compared with 75% in homozygous FCGR3B-NA2 and 75% in heterozygous patients (not significant). We found no difference for progression-free and overall survival by FCGR3B-NA1/NA2 genotypes.

Conclusion: These results indicate no association between FCGR3B-NA1/NA2 polymorphism and response to rituximab indicating no significant role of phagocytosis mediated by neutrophils in in vivo mechanism of rituximab activity.

Patients and methods: This report concerns prospectively recorded cases that were either treated at Institut Gustave Roussy (Villejuif, France) or referred there for advice about therapy. From 1990 to 2006, 52 patients underwent surgery followed by BEP chemotherapy. Data on patient characteristics, treatment, survival, and fertility outcome were analyzed to assess treatment efficacy and gonadal toxicity after achieving a complete remission.

Results: Thirty-five patients had stage I/II tumors while 17 patients presented with stage III/IV disease. With a median follow-up of 68 months, the overall 5-year survival and disease-free survival rates were 94% and 90%, respectively. Forty-one women underwent fertility-sparing surgery. Pregnancy was achieved in 12 of 16 (75%) women who attempted conception. Overall, 19 pregnancies have been recorded.

Conclusions: BEP chemotherapy following fertility-sparing surgery is a very effective treatment of ovarian YSTs. Most of the patients who attempt conception after complete remission will have children.

Patients and methods: A total of 649 patients received IFN 9 MIU s.c. three times weekly plus bevacizumab 10 mg/kg or placebo every 2 weeks until disease progression. The IFN dose was reduced to 6 or 3 MIU with the development of IFN-attributed toxicity. Differences between treatment arms in PFS, response rate and tolerability were analysed in the reduced-dose group.

Results: IFN dose was reduced in 131 patients in the bevacizumab + IFN arm and 97 patients in the IFN + placebo arm during the trial. PFS rates in the bevacizumab + reduced-dose IFN group were comparable with the total population (Kaplan–Meier estimates of event-free rate at 1 year: 0.524 versus 0.427). Bevacizumab + reduced-dose IFN was well tolerated, with substantial decreases in the rate of adverse events following dose reduction.

Conclusion: This retrospective subgroup analysis suggests that the dose of IFN can be reduced to manage side-effects while maintaining efficacy in patients with mRCC receiving bevacizumab + IFN.

Patients and methods: Tamoxifen and 4-hydroxytamoxifen (4OHtam) were measured in the serum of 37 women with breast cancer who were receiving tamoxifen treatment. The association between CYP2D6 *10 genotype and survival was determined in a cohort of 293 women with breast cancer who received tamoxifen (n = 152) or who did not (n = 141).

Results: The serum 4OHtam concentrations were significantly lower in women with the CYP2D6 *10 homozygous variant T/T genotype than in those with the homozygous wild-type C/C genotype (P = 0.04). Among tamoxifen-treated women, women with the T/T genotype had a significantly worse disease-free survival (DFS) than those with the C/C or C/T genotype, and the T/T genotype remained an independent prognostic factor of DFS in multivariate analysis (hazard ratio = 4.7; 95% confidence interval = 1.1–20.0; P = 0.04). Among women who did not receive tamoxifen, there was no significant association between CYP2D6 *10 genotype and survival.

Conclusion: In tamoxifen-treated patients, women with the CYP2D6 *10 T/T genotype have a lower 4OHtam level in the serum and a worse clinical outcome.

Design: Thirty-two pts received MMC i.v. 6 mg/m² day 1 and CPT-11 i.v. 125 mg/m² days 2 and 8 every 28 days for maximum of six cycles. TOPO I expression and NQO1 reductase genotyping in 23 of 32 (72%) pts were assayed by PCR.

Results: The median time to progression (TTP) was 4.7 months (95% confidence interval 4.0–5.4 months). TOPO I expression was increased 5- to 10-fold and 20- to 30-fold in PBMC at 24 and 168 h, respectively. There was no relationship between these markers and efficacy or toxicity of the regimen.

Conclusions: Sequential low-dose MMC and CPT-11 was active and tolerable by pretreated MBC pts. Future trials should focus on less pretreated MBC pts and sequential tumor biopsies to test the hypothesis that increased intratumoral expression of TOPO I is related to efficacy.

Materials and methods: All published clinical trials stopped early for benefit and published in the last 11 years, regarding anticancer drugs and containing an interim analysis, were assessed.

Results: Twenty-five RCTs were analysed. The evaluation of efficacy was protocol planned through time-related primary end points, >40% of them overall survival. In 95% of studies, at the interim analysis, efficacy was evaluated using the same end point as planned for the final analysis. As a consequence of early stopping after the interim analysis, ~3300 patients/events across all studies were spared. More than 85% of the RCTs published in the last 3 years were used for registration purposes.

Conclusion: Though criticism of the poor quality of oncological trials seems out of place, unfortunately early termination raises new concerns. The relation between sparing patients and saving time and trial costs indicates that there is a market-driven intent. We believe that only untruncated trials can provide a full level of evidence which can be translated into clinical practice without further confirmative trials.

Patients and methods: Standard questionnaires were used to determine the psychological impact suffered by patients who underwent IBR, DBR and no reconstruction, their degree of satisfaction with the results achieved, and their postprocedure opinions regarding reconstruction options.

Results: A total of 526 women underwent mastectomy. The response rate to the questionnaires was 71.67%. A significantly greater proportion of the women who underwent no reconstruction suffered psychological problems than those who underwent reconstruction of some type (P = 0.01). Some 94.77% of the women who underwent IBR maintained a postprocedure preference for this option; in contrast, some 87.27% of the DBR and 56.14% of the no-reconstruction patients declared a postprocedure preference for IBR. In all, 63.49% of the women who underwent reconstruction were moderately very satisfied with the aesthetic results achieved, while only 22.80% of the no-reconstruction patients declared such satisfaction (P = 0.0001).

Conclusions: The women who underwent no breast reconstruction suffered more emotional problems than those who underwent a reconstruction procedure. In general, all groups reported a postprocedure preference for IBR in their questionnaire answers. The aesthetic results achieved by IBR seem to be those best accepted.

Materials and methods: The involvement of C-MYC in MTX resistance was validated with an antisense approach. C-MYC and DHFR protein levels at diagnosis were assessed by immunohistochemistry on series of patients treated with either a MTX-based protocol (IOR/OS-1; 72 patients) or with a standard four-drug regimen (ISG/SSG 1; 61 patients).

Results: Down-regulation of C-MYC significantly decreased the MTX resistance level of OS cells, demonstrating its causal involvement in this phenomenon. In clinical samples, a worse outcome was associated with increased levels of DHFR and C-MYC at diagnosis in the IOR/OS-1 patients and of C-MYC in the ISG/SSG 1 patients.

Conclusions: Meanwhile the adverse clinical impact of DHFR overexpression appeared to be closely related to the relevance of MTX in the chemotherapeutic protocol, that of C-MYC overexpression was more general and not strictly MTX related. The assessment of C-MYC and DHFR at diagnosis, together with that of other known prognostic markers, can be considered for an early identification of subgroups of OS patients with higher risk of adverse outcome.

Patients and methods: Two hundred and eighty patients newly diagnosed as NTCL were enrolled from 22 Korean medical centers. Two subsets were compared: one involving the upper aerodigestive tract (UAT) and another involving the non-upper aerodigestive tract (NUAT) region, which comprises the skin, gastrointestinal tract, and liver or soft tissues. Clinical prognostic factors, survival outcomes, and independent predictors for survival were compared between each subset.

Results: NUAT-NTCL (59 patients) had significantly higher proportions of disseminated disease, aggressive biologic features, and unfavorable host reactions compared with UAT-NTCL (221 patients). NUAT-NTCL had shortened 5-year overall survival (OS) (22% versus 41%, P = 0.001). Ann Arbor staging, the International Prognostic Index, and the NTCL prognostic index failed to predict the OS of NUAT-NTCL, but did predict the OS in UAT-NTCL. Independent predictors for OS by multivariate analyses differed between each subset. In the NUAT subset, extranodal sites and regional nodes predicted the OS, while Ann Arbor staging, age, performance status, and lactate dehydrogenase level predicted the OS in the UAT subset.

Conclusion: NUAT-NTCL may represent a distinctive disease entity in terms of clinical factors, independent predictors, and survival outcomes.

Patients and methods: International Breast Cancer Study Group Trial VI accrued 1475 eligible pre- and perimenopausal women with node-positive breast cancer who were randomly assigned to receive three to nine courses of classical combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. ECS status was determined retrospectively in 933 patients based on review of pathology reports. Cumulative incidence and hazard ratios (HRs) were estimated using methods for competing risks analysis. Adjustment factors included treatment group and baseline patient and tumor characteristics. The median follow-up was 14 years.

Results: In univariable analysis, ECS was significantly associated with supraclavicular recurrence (HR = 1.96; 95% confidence interval 1.23–3.13; P = 0.005). HRs for local and axillary recurrence were 1.38 (P = 0.06) and 1.81 (P = 0.11), respectively. Following adjustment for number of lymph node metastases and other baseline prognostic factors, ECS was not significantly associated with any of the three recurrence types studied.

Conclusions: Our results indicate that the decision for additional regional radiotherapy should not be based solely on the presence of ECS.

Patients and methods: Patients with either a cisplatin absolute-refractory GCT defined as progressive disease (PD) during or within 1 month of CDDP administration or with a poor prognosis relapse, defined as PD between the second and the sixth month after CDDP administration, were treated with a combination of oxaliplatin (130 mg/m²) and paclitaxel (175 mg/m²) administered every 21 days. Primary end point was efficacy.

Results: Twenty-seven patients were included. Patients were pretreated with a median of two lines of cisplatin-based chemotherapy (range 1–5). Sixteen patients were absolute refractory. Five patients had relapsed after high-dose chemotherapy plus stem-cell support. There were no complete responses but there was one marker-positive partial response and nine disease stabilization (34, 6%). After a median follow-up of 65 months, two patients are disease-free survivors. Main toxicity was leucocytopenia grade 3/4 in 30% of the patients.

Conclusion: Combination chemotherapy with oxaliplatin and paclitaxel is feasible with acceptable toxicity and may be effective if combined with additional treatment in patients with CDDP-refractory GCT.

Patients and methods: Patients with advanced RCC, no prior systemic therapy, and three or more of six poor-risk factors were randomly assigned to one of three groups: (i) IFN s.c. up to 18 MU thrice weekly, (ii) temsirolimus i.v. 25 mg weekly, or (iii) temsirolimus i.v. 15 mg weekly plus interferon s.c. 6 MU thrice weekly.

Results: Among 208 patients, the most common temsirolimus-related grades 3–4 AEs were anemia (13%), hyperglycemia (9%), and asthenia (8%). Grades 3–4 hypercholesterolemia (1%), hypertriglyceridemia (3%), and hypophosphatemia (4%) were also seen. Although pneumonitis occurred infrequently, vigilance for its development is needed. Guidelines for management of toxic effects are presented on the basis of available clinical experience.

Conclusions: Temsirolimus-related grades 3–4 AEs were primarily metabolic in nature and easily controlled medically. In general, these did not negatively impact patient quality of life.

Patients and methods: A consecutive series of 32 cancer patients with mild to severe persistent fatigue [scores on the Brief Fatigue Inventory (BFI) > 25] participated in a 3-week exercise program consisting of endurance (30 min walking on a treadmill) and resistance/coordination exercises for the major muscle groups. Fatigue, mood, and anxiety were assessed with questionnaires and physical performance with a stress test before and after the program.

Results: At the end of the program, we observed a significant increase of physical performance (workload at the anaerobic threshold pre 61 ± 26 W, post 78 ± 31 W, P < 0.0001) and reduction of global fatigue (Functional Assessment of Cancer Therapy: pre 45.7 ± 13.4, post 52.6 ± 12.4, P < 0.0001; BFI: pre 37.9 ± 18.3, post 31.2 ±17.1, P < 0.001). However, no significant improvement of cognitive fatigue or reduction of anxiety was observed.

Conclusions: A 3-week exercise program leads to a substantial improvement of physical performance and reduction of mental and physical fatigue in cancer patients after treatment. However, this intervention does not affect depression, anxiety, or cognitive fatigue.

Methods: We undertook a review of published articles and abstracts relating to clinical studies of UFT in the treatment of locally advanced rectal cancer (LARC). Pre- and postoperative studies carried out in patients with newly diagnosed or recurrent disease were included.

Results: The combination of UFT and radiotherapy was effective and well tolerated in the preoperative setting, while adjuvant UFT improved survival and reduced distant relapse compared with surgery alone. The efficacy of UFT appears comparable with that of 5-FU and capecitabine and its side-effect profile is favourable.

Conclusion: Clinical experience to date suggests that UFT is a valuable treatment option for the perioperative treatment of LARC. Further improvements in patient outcomes may result from the combination of UFT with targeted agents.

Patients and methods: Patients were stratified by response to prior taxane therapy (resistant or nonresistant). Larotaxel 90 mg/m² was administered as a 1-h infusion every 3 weeks. Patients were evaluated for tumor response every two cycles. A blinded external response review committee determined the overall response rate (ORR), duration of response (DOR), and time to progression (TtP) of the disease. Median survival time (MST) and safety were also evaluated.

Results: One hundred and thirty patients were treated. In the nonresistant group, the ORR was 42%; median DOR 5.3 months; median TtP 5.4 months; and MST 22.6 months. In the resistant group, the ORR was 19%; median DOR 5.0 months; median TtP 1.6 months; and MST 9.8 months. The most common grade 3/4 adverse events were neutropenia (82%), fatigue (15%), diarrhea (12%), febrile neutropenia (9%), neutropenic infection (8%), and sensory neuropathy (7%).

Conclusions: Larotaxel has good activity, manageable toxicity, and a favorable therapeutic index in women with taxane-pretreated MBC.

Patients and methods: We studied the immunohistochemical expression of IGF1 receptor (IGFR-I), IGF1 and IGF2 in 94 samples of GISTs. IGF1 and IGF2 expression was scored in three classes: negative (N), moderate (M) and strong (S), according to staining intensity and extent.

Results: IGFR-I was overexpressed in all cases. IGF1 and IGF2 expression was absent in 25 and 48 cases, moderate in 29 and 16 cases and strong in 40 and 30 cases, respectively. Strong IGF1 expression significantly correlated with higher mitotic index (P = 0.0001), larger (P = 0.01), higher risk (P = 0.0002), metastatic (P = 0.0001) and relapsed (P = 0.04) GISTs. Strong IGF2 expression correlated with higher mitotic index (P = 0.05) and higher risk GISTs (P = 0.001). The Kaplan–Meier analysis (N versus M versus S) showed a significant worsening of the disease-free survival (DFS) with the increase of IGF1 (P = 0.02) and IGF2 (P = 0.02) expression. In the subgroup of patients with operated high-risk GISTs, there was a better trend in DFS for patients affected by GISTs with negative IGF1 and IGF2.

Conclusions: The expression of IGF1 and IGF2 seems to predict relapse in GIST patients.

Patients and methods: In total, 348 adult patients [62 gastric adenocarcinoma, 45 PUD and 241 nonulcer dyspepsia (NUD)] who underwent an upper gastrointestinal endoscopy were enrolled. PPAR polymorphism was analyzed by PCR-based restriction fragment length polymorphism. H. pylori infection was diagnosed by rapid urease test, culture, histopathology and PCR.

Results: PPAR G carrier had significant association with gastric adenocarcinoma [P = 0.023, odds ratio (OR) = 2.136, 95% CI = 1.112–4.104] and PUD (P = 0.028, OR = 2.165, 95% CI = 1.008–4.306) when compared with NUD. Combination of G carrier and H. pylori infection further increased the risk of gastric adenocarcinoma (OR = 3.054, 95% CI = 1.195–7.807) and PUD (OR = 11.161, 95% CI = 3.495–35.644). PPAR polymorphism did not increase the risk of gastric adenocarcinoma and PUD in H. pylori-negative subjects.

Conclusions: The study suggests that Pro12Ala PPAR polymorphism is associated with gastric adenocarcinoma and PUD, and is a potential marker for genetic susceptibility to these two diseases in the presence of H. pylori infection.

Patients and methods: Prognostic values of different pretherapeutic features were tested in univariate and multivariate analyses in a population of 301 NSCLC.

Results: Median survival was 17 months. One-third of patients reporting difficulties in their normal daily activities and an overall poor QoL. The following pretreament variables were independent determinants of a shorter overall survival: advanced disease, SCS, Lung Cancer Symptoms Scale global symptoms score, anaemia, hyponatremia, serum alkaline phosphatases level, serum CYFRA 21-1 and serum neuron-specific enolase.

Conclusion: In this extended validation population, the SCS is more informative than the CCI in predicting NSCLC patient outcome as the former is also more disease specific. Combination of both SCS comorbidity score and LSCC QoL yields a more accurate information that conventional analysis of PS.

Patients and methods: Serum PSA levels were monitored every 3 weeks in 79 patients with CRPC treated with chemotherapy and a time course of serum PSA levels was obtained. Correlation with response was studied.

Results: According to consensus criteria, 21 (40%) and 20 (38%) patients achieved a PSA response and stabilization, respectively, after first-line chemotherapy. Among patients who achieved either a response or a stabilization, 8 of 41 (20%) had a serum PSA rise during the first 8 weeks of chemotherapy, followed by a subsequent decline in serum PSA. The same observation was made in patients receiving second-line chemotherapy: 6 of 20 patients achieving a response or stabilization had an initial serum PSA rise. The postchemotherapy increase in serum PSA could reach more than twice the baseline value. The duration of the PSA surge ranged from 1 to 8 weeks. When considering responders only, 6 of 30 (20%) had a postchemotherapy serum PSA surge, followed by a drop.

Conclusion: Postchemotherapy PSA surges occur not infrequently in patients with CRPC who respond to chemotherapy. Physicians should be aware of this effect to avoid inadequate early discontinuation of chemotherapy.

Patients and Methods: Demographic and clinicopathologic data were obtained from the Tokai Ovarian Tumor Study Group between 1986 and 2006. Survival curves were calculated using the Kaplan–Meier method. Differences in survival rates were analyzed using the log-rank test.

Results: A total of 205 patients had clinical pTI–IIb CCC (median age: 52 years, range: 30–75). One hundred and four (50.7%) patients underwent systemic retroperitoneal lymphadenectomy. Lymphadenectomy was not associated with improved disease-free and overall survival in all patients (P = 0.353 and P = 0.645, respectively). Moreover, lymphadenectomy did not improve the overall survival in those with pTIc CCC (P = 0.433). Similarly, on univariate analysis, age, volume of ascites, preoperative CA 125 values, and regimen of chemotherapy were