Annals of Oncology Advance Access originally published online on November 15, 2006
Annals of Oncology 2007 18(2):263-268; doi:10.1093/annonc/mdl376
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© 2006 European Society for Medical Oncology
gynecologic tumors |
Second-line chemotherapy with pegylated liposomal doxorubicin and carboplatin is highly effective in patients with advanced ovarian cancer in late relapse: a GINECO phase II trial
1 Centre Antoine Lacassagne, Nice
2 Centre Alexis Vautrin, Vandoeuvre-Les-Nancy
3 Hôpital Hôtel-Dieu, Paris
4 Clinique Pasteur, Evreux
5 Hôpital Fleyriat, Bourg-en-Bresse
6 Centre Hospitalier, Le Mans
7 Centre Georges François Leclerc, Dijon
8 Centre Hospitalier, Brive-La-Gaillarde
9 CHU Bretonneau, Tours
10 Université Paris Descartes, Paris, France
* Correspondence to: Dr E. Pujade-Lauraine, Département d'Hématologie et d'Oncologie Médicale, Hôpital Hôtel-Dieu, 1 Place du Parvis Notre Dame, 75004 Paris, France. Tel: +33-142-34-80-28; Fax: +33-142-34-81-10; E-mail: epujade{at}gineco.org
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Abstract |
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Background: Platinum-based chemotherapy is standard second-line treatment of patients with advanced ovarian cancer (AOC) in late relapse. Pegylated liposomal doxorubicin (PLD) has significant single-agent activity in this setting. Therefore, we evaluated the use of PLD plus carboplatin in this patient population.
Patients and methods: PLD 30 mg/m2 followed by carboplatin at area under the curve (AUC) 5 mg·min/ml, repeated every 28 days for a maximum of nine cycles, was administered to 104 women with AOC relapsing 
6 months after completion of first- or second-line therapy with platinum-taxane-based regimens.
Results: Overall response was 63%, with a 38% complete response, median progression-free survival of 9.4 months, and median overall survival (OS) of 32 months. Grade 3 or 4 neutropenia occurred in 51% of patients, but febrile neutropenia in only 3%. Nonhematologic toxic effects were primarily grades 1 and 2, with low rates of alopecia and neurotoxicity.
Conclusions: PLD plus carboplatin is highly effective, prolongs OS, and is well tolerated in women with AOC in late relapse previously treated with both platinum and taxanes. Evaluation of this regimen in phase III trials is warranted.
Key words: liposomal doxorubicin, ovarian cancer
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introduction |
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TopAbstractintroductionpatients and methodsresultsdiscussioncontributorsAcknowledgementsReferences |
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Patients with advanced ovarian cancer (AOC) that relapses >6 months after completion of initial platinum-based chemotherapy are considered by many clinicians to be good candidates for re-treatment with a platinum-based regimen. Until recently, there has been no evidence of improved survival for combination versus single-agent platinum regimens in these women with AOC in late relapse. In the first large clinical trial to demonstrate a survival advantage when comparing platinum-containing regimens for AOC (ICON4-OVAR 2.2), there was an absolute difference in 2-year survival of 7% (57% versus 50%) and in median survival of 5 months (29 versus 24 months) favoring platinum plus paclitaxel (Taxol) over conventional platinum-based chemotherapy (primarily carboplatin alone) [1].
A potential barrier to using a platinum–taxane combination in women with AOC in late relapse is that many will have received first-line treatment with a platinum–taxane combination [2–11] and experienced adverse events including neurotoxicity and alopecia [1, 12]. They may, therefore, be at risk for more serious neurologic events if re-treated with a taxane. They also may be reluctant to experience hair loss again at the time of relapse. Therefore, efforts are underway to develop platinum combinations that are equally effective as platinum–taxane, but with less alopecia and neurotoxicity.
Pegylated liposomal doxorubicin (PLD; Caelyx, Schering-Plough International, Kenilworth, NJ) has a longer circulation time than conventional doxorubicin, allowing for lower peak plasma concentrations and increased tumor concentration of drug. Tumor concentrations of doxorubicin are 4- to 11-fold higher with PLD versus conventional doxorubicin [13, 14]. Main limiting toxic effects with PLD are skin and mucosal toxic effects, which are linked to the dose and dose interval. Alopecia, nausea, vomiting, and hematologic toxic effects are less common than with the conventional product, and cardiotoxicity is rare [15, 16].
Single-agent efficacy of PLD in ovarian cancer was demonstrated in two phase III studies comparing PLD with paclitaxel [17] or topotecan (Hycamtin) [18, 19] as second-line therapy. In the first study, there were no significant efficacy differences between PLD and paclitaxel, regardless of platinum sensitivity. Toxicity profiles, however, differed, leading the authors to suggest that PLD may be advantageous for patients with musculoskeletal disorders or in whom alopecia was to be avoided [17]. In the comparison of PLD with topotecan, overall survival (OS) was superior with PLD (63 versus 60 weeks, P = 0.05), particularly in platinum-sensitive patients (112 versus 77 weeks, P = 0.002) [18]. In addition, PLD had a more favorable safety profile and a less cumbersome administration schedule [17, 18].
The single-agent efficacy of PLD [17–19] and carboplatin [1] and evidence from the ICON4-OVAR 2.2 study demonstrating that combination platinum-containing regimens are superior to single-agent platinum regimens [1] support an evaluation of combination therapy with PLD and carboplatin for ovarian cancer. On the basis of these favorable data, we investigated the efficacy and tolerability of combination therapy with PLD and carboplatin in women with AOC in late relapse who were pretreated with platinum and a taxane.
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patients and methods |
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study design
This open-label, multicenter, phase II study evaluated the antitumor efficacy and safety of combination therapy with PLD plus carboplatin (Paraplatin, Bristol Myers Squibb Company) in patients with late-relapsing (>6 months after last chemotherapy) ovarian cancer. Patients relapsed after completion of first- or second-line therapy with a platinum-taxane-based regimen. All patients provided signed informed consent. The study was approved by the ethics committee and conducted in accordance with the ethical principles that originated in the Declaration of Helsinki.
eligibility criteria
Eligible patients were 18 years old and had histologically confirmed primary ovarian adenocarcinoma with peritoneal or visceral metastatic disease and disease progression 6 months after the end of the last chemotherapy treatment. Prior treatment with two or less lines of chemotherapy, one of which included but was not limited to a platinum and a taxane, was required. While prior treatment with hormone therapy, immunotherapy, or radiotherapy was permitted, all such treatments were discontinued at least 4 weeks before study entry. Other eligibility criteria included measurable lesions and/or a CA 125 40 IU/ml and an Eastern Cooperative Oncology Group performance status 
2.
Patients were excluded from the study if they had prior bone marrow autograft or total abdominal irradiation. Other exclusion criteria were history of heart disease; cerebral or meningeal metastases or other malignant tumor, except curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; and inadequate renal [serum creatinine clearance >1.25 x the upper limit of normal (ULN)], liver (serum bilirubin >1.25 x ULN and serum transaminase levels >2 x ULN in the absence of liver metastases or >5 x ULN with liver metastases), or hematologic function (white blood cell count <4.0 x 109/l, granulocyte count <2.0 x 109/l, and platelets <100 x 109/l). Women who were pregnant, breast-feeding, or of reproductive age and not using adequate contraception were excluded.
treatment plan
PLD 30 mg/m2 was infused over 1 h. After completion of the PLD infusion, carboplatin at area under the curve (AUC) 5 mg·min/ml (Calvert formula [20]; maximum dose of 800 mg in patients with a creatinine clearance >135 ml/min) was infused over 30 min. Treatment was repeated every 28 days. Antiemetics, including corticosteroids, were permitted. A cooling cap was recommended during carboplatin administration in an attempt to reduce the risk and severity of alopecia. The use of hematopoietic growth factors was at the discretion of the investigator.
In the absence of unacceptable toxicity or disease progression, treatment was administered for at least two cycles. In patients with stable disease or response after cycle 2, treatment was continued at the discretion of the investigator for a maximum of nine cycles or until unacceptable toxicity.
Drug dosage was modified as a function of hematologic nadir, hematologic recovery, skin toxicity, or mucosal toxicity. In patients experiencing any other National Cancer Institute (NCI) common toxicity criteria (CTC) version 2.0 grade 3 or greater toxicity, with the exception of nausea and vomiting, dosage adjustment or treatment discontinuation was at the discretion of the investigator. Patients requiring more than one dose reduction for the same drug were discontinued from the study treatment.
For a granulocyte count <0.5 x 109/l (CTC grade 4) for 7 days, a granulocyte count <0.1 x 109/l for 3 days, an episode of febrile neutropenia (defined as temperature 38.5°C at two independent measurements and granulocyte count <1 x 109/l), an infection requiring intravenous antibiotics and/or hospitalization, platelet count <25 x 109/l, or bleeding that required a platelet transfusion, the dose of PLD was reduced to 25 mg/m2 and carboplatin to AUC 4 mg·min/ml.
Treatment was held for a granulocyte count <1.5 x 109/l and a platelet count <100 x 109/l. If hematologic recovery was achieved between days 35 and 42, PLD and carboplatin doses were reduced as above. If hematologic recovery was inadequate by day 42, the patient was removed from the study. In patients experiencing skin or mucosal toxicity (any grade), treatment was withheld until the toxicity resolved. Treatment was subsequently restarted or discontinued based on preestablished guidelines (Table 2).
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clinical, laboratory, and radiologic assessments
Before study entry, clinical, laboratory, and radiologic assessments were carried out. Clinical assessment included complete medical history, physical examination, weight, height, performance status, and electrocardiogram. Laboratory measurements included complete blood cell count with differential, creatinine clearance, serum bilirubin level, transaminase levels, alkaline phosphatase levels, and CA 125 levels. Radiologic assessment included chest X-ray, abdominal–pelvic scan (magnetic resonance imaging or ultrasound), and ventricular ejection fraction by echogram or scan. Differential blood count was done at least weekly thereafter and clinical and other laboratory assessments, including CA 125 levels, were repeated before each treatment. Chest X-ray and abdominal–pelvic scan were repeated at least every two cycles.
efficacy assessment
The primary efficacy variable was overall or objective response (OR), which was assessed every two cycles. In patients achieving an OR, confirmation was recommended at a second analysis at least 4 weeks after OR was initially identified. Patients with at least one measurable lesion were evaluated for response according to standard World Health Organization (WHO) efficacy criteria. Nonmeasurable lesions were categorized as evaluable or not evaluable. Each OR was reviewed by an independent panel.
In patients with measurable disease, a clinical complete response (CR) was defined as the complete disappearance of all signs of measurable or evaluable disease with CA 125 level normalization for at least 4 weeks. Partial response (PR) was defined as per WHO efficacy criteria. Patients who showed neither a CR nor a PR were considered nonresponders.
Patients with nonmeasurable disease and CA 125 levels 40 IU/ml were evaluated according to Rustin's criteria [21]. Evaluation required at least four CA 125 samples, with the first taken between 9 and 35 days after the first cycle of chemotherapy. This first level must have been 40 IU/ml for inclusion in the analysis. A serologic response was achieved if the CA 125 level from samples 2 and 3 was 50% lower than in the first sample. This response must have been confirmed by a fourth sample taken at least 28 days after the preceding one. The serologic response was considered complete (i.e. serologic CR) when the CA 125 level was normalized for at least 28 days.
Patients were not assessable if they had no measurable disease and a CA 125 level <40 IU/ml (ineligible) or a CA 125 level 40 IU/ml and less than four samples available for evaluation. When insufficient samples were related to early disease progression, patients were classified as having progressive disease (PD).
Secondary efficacy variables included progression-free survival (PFS) and OS. PFS was calculated from the first day of treatment to the date of progression or death from any cause. PD was defined as an increase of 25% or more in existing lesions, and/or the appearance of new lesions, and/or serologic progression according to Gynecologic Cancer Intergroup (GCIG) criteria [22]. OS was calculated from the first day of treatment to the date of death.
safety assessment
Safety was evaluated during each cycle. Using NCI CTC version 2.0, the highest grade of toxicity encountered during treatment was recorded before each cycle and during follow-up. Follow-up visits were planned every 3 months for 2 years, then every 6 months for 5 years or until death. All patients receiving at least one cycle of treatment were assessable for toxicity.
statistical analysis
The sample size was determined for analysis of the primary end point, OR, using a stepwise approach according to O'Brien and Fleming [23]. Because there is contradictory experience regarding the impact of the number of lines of treatment on response, patients were divided into two groups, those receiving treatment as second-line therapy and those receiving treatment as third-line therapy. In patients receiving treatment as second-line therapy, accepting alpha and beta risks on the order of 5% and assuming that the treatment must be considered ineffective below an OR of 30%, an OR of 50% was established as the cut-off. Interim analysis of OR was carried out after 15 and 30 patients were enrolled. If an OR 80% was observed at the time of either interim analysis, the study was stopped and the combination considered effective. If the response rate was 20%–79%, 15 additional patients were treated. If a response rate of 19% was observed, the study would be stopped and the combination considered ineffective. Using this approach, a sample size of 45 patients was required.
A similar approach was used in patients receiving third-line treatment. Accepting alpha and beta risks of 5% and assuming that below a response rate of 20% the treatment would be considered ineffective, a response rate of 40% was established as the cut-off.
Assuming 45 assessable patients and seven ineligible patients per group, a sample size of 104 was considered adequate for analysis of the primary end point. All eligible patients receiving at least one cycle of study treatment were assessable for response. Efficacy was analyzed as a function of the number of prior lines of chemotherapy and treatment-free interval (TFI; i.e. 6–12 months or 12 months).
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results |
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A total of 105 patients were enrolled in the study, of which 104 received treatment (Table 1). Measurable lesions were reported in 57% of patients and 42% had more than one metastatic site. Baseline CA 125 levels
40 IU/ml were reported in 86% of patients; 39% had no measurable lesion at baseline but had elevated CA 125 levels. All patients had been pretreated with platinum and taxane, and 64% achieved a CR to prior treatment. Second-line therapy included a platinum in 59% of patients and a taxane in 56%.
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Patients received a median of six cycles of PLD–carboplatin chemotherapy (range, 1–10). The median doses of PLD and carboplatin were 97% and 95%, respectively, of the planned doses. Granulocyte colony-stimulating factor, red blood cells, or platelets were required in 16%, 12%, and 3% of patients, respectively. Dose reduction and course delay, due mainly to delays in hematologic recovery, were observed in 33% and 54% of patients and 7% and 20% of cycles, respectively.
efficacy
This intention-to-treat efficacy analysis was based on 104 patients, including four patients not assessable for response as they had no measurable lesion or CA 125 levels 40 IU/ml at baseline and five patients with major eligibility criteria violations. Four of these patients had a TFI <6 months (actual, 5 months) and one received three lines of prior chemotherapy.
OR was similar in the overall population and in women with and without measurable disease (60%–65%) (Table 3), as well as in patients receiving second-line treatment (66%) and third-line treatment (65%).
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Median PFS for the total patient population was 9.4 months and was independent of the presence or absence of measurable disease. Median PFS was 9.5 months for patients treated with second-line and 9.2 months for patients treated with third-line therapy. Patients with a TFI <12 months, however, had a significantly lower median PFS (7.9 months) than patients with TFI
12 months (11.4 months, P = 0.001) (Figure 1).
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A longer TFI also was associated with significantly longer OS (Figure 2). Median OS was 32 months for the entire group. In women with a TFI
12 months, median OS was 36 months compared with 21 months in women with a TFI of 6–12 months (P = 0.006, log-rank).
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safety
Thirteen of the 104 patients assessable for safety discontinued treatment prematurely due to toxicity, including hematologic toxicity (n = 4), hematologic toxicity and PD (resulting in death, n = 2), hand food syndrome (HFS, n = 2), hypersensitivity (n = 2), and patient convenience (n = 3).
Hematologic toxicity was more common than nonhematologic toxicity. During 527 evaluable cycles, grade 3 or 4 neutropenia was reported in 51%, leukopenia in 27%, thrombocytopenia in 26%, and anemia in 12% of patients. Febrile neutropenia was reported in 3% of patients.
Nonhematologic adverse reactions were primarily grade 1 or 2; there were no grade 4 nonhematologic adverse reactions (Table 4). More than 50% of patients experienced nausea and vomiting or asthenia. Palmar/plantar erythrodysesthesia was reported in one-third of patients, but was grades 1 and 2 only. Most alopecia was grade 1. No clinical evidence of cardiotoxicity was observed during the study.
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discussion |
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The potential for platinum sensitivity is one of the most important factors in making treatment decisions in relapsed AOC. Tumor response to most agents is related to platinum-free interval. Since the median progression-free interval after initial therapy with platinum–paclitaxel is 16–22 months, most patients are categorized as having late relapse and considered platinum sensitive. These patients are generally re-treated with platinum–paclitaxel at first relapse but, because most toxic effects are cumulative, are at increased risk of neurotoxicity and myelosuppression [24].
While prolonging survival is an important consideration in treatment selection, other factors should also be considered. Since the treatment of relapsed AOC is rarely curative, tolerability, convenience of administration, and quality of life should be considered as well. We demonstrate here that combination therapy with PLD (30 mg/m2) and carboplatin (AUC 5 mg·min/ml) yields a high OR (63%) and is well tolerated in patients with AOC in late relapse. Moreover, OR based on WHO criteria (60%) was similar to OR based on changes in CA 125 (65%). As would be expected, PFS and OS increased in patients with a longer TFI. Hematologic toxicity was moderate. There was a low incidence of both alopecia and neurotoxicity, with HFS limited to grades 1 and 2. Treatment is conveniently administered at 4-week intervals. Others schedules of the combination using higher doses of carboplatin and/or PLD have been reported in small series of ovarian cancer patients [25, 26]. A direct comparison between these different schedules of PLD–carboplatin would be necessary to determine whether the expected augmentation of toxicity induced by higher drug dosages within the combination might translate into better efficacy.
While we acknowledge the difficulties associated with comparing results across studies, our data are similar to those reported for the carboplatin–paclitaxel arm of the ICON4-OVAR 2.2 study [1]. Despite poorer performance status, a greater number of previous chemotherapy treatments (including paclitaxel), and more patients relapsing within 12 months in our study, the 32-month median survival reported here compares with the median survival of 29 months for platinum–taxane in ICON4-OVAR 2.2. Although PFS was 12 months in the ICON4-OVAR 2.2 study versus 9.4 months in our study, the criteria for PFS differed. In our study, progression criteria included an isolated elevation of CA 125 levels. In the ICON4-OVAR 2.2 study, a raised CA 125 level in the absence of clinical or radiologic evidence of PD was not considered PD.
Toxic effects were also notably different with platinum–taxane in ICON4-OVAR 2.2 [1] compared with our findings with PLD–carboplatin. Grade 2 or greater neurotoxicity (7% with PLD–carboplatin versus 20% with platinum–taxane) and alopecia (12% versus 86%, respectively) were more common with platinum–taxane, while mucositis (12% versus 8%, respectively) and HFS (11% versus 0%, respectively) were more common with PLD–carboplatin.
These data support the clinical efficacy and tolerability of PLD in combination with carboplatin for second-line therapy of AOC in late relapse. A phase III intergroup study is being conducted to confirm our findings. It will compare PLD plus carboplatin with paclitaxel plus carboplatin for recurrent epithelial ovarian or peritoneal carcinoma in women in late relapse after failure of initial platinum-based chemotherapy and with limited neurotoxicity from prior treatment. Ongoing trials are also evaluating platinum–taxane–PLD triplets as a strategy to improve survival after first-line therapy.
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contributors |
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The following individuals contributed to this study: Abadie-Lacourtoisie S, Centre Paul Papin, Angers; Abraham C, CH de Versailles, Le Chesnay; Agostini C, Hôpital de Chambéry, Chambéry; Albin N, Clinique Pasteur, Evreux; Assouline D, Clinique du Mail, Grenoble; Ayela P, Centre Hospitalier, Lourdes; Bachmeyer C, Centre Hospitalier Laennec, Creil; Barats JC, Hôpitaux Civils de Colmar, Colmar; Barletta H, Clinique Générale de Valence, Valence; Boaziz C, Clinique Claude Bernard, Ermont; Botton E, Hôpital Morvan, Brest; Botton A, Clinique Sainte Marie, Pontoise; Bouffette P, Hôpital Américain, Neuilly sur Seine; Callet B, Hôpital Américain, Neuilly sur Seine; Chauvenet L, Hôpital Hôtel-Dieu, Paris; Chinet-Charrot P, Centre Henri Becquerel, Rouen; Coeffic D, Clinique du Mail, Grenoble; Cretin J, Clinique Rochebelle, Ales; Dahan O, Polyclinique Bordeaux Nord, Bordeaux; De Gislain C, Centre Georges François Leclerc, Dijon; Delva R, Centre Paul Papin, Angers; Dohollou N, Polyclinique Bordeaux Nord, Bordeaux; Dor J-F, CH d'Antibes-Juan-Les-Pins, Antibes; Edel M, Hôpital Emile Muller, Mulhouse; Fargeot P, Centre Georges François Leclerc, Dijon; Favre R, Hôpital de la Timone, Marseille; Favre A, Centre Hospitalier La Source, Orléans; Fleck E, Centre Hospitalier de la Rochelle, La Rochelle; Flesch M, Clinique Fondation Clément Drevon, Dijon; Freyer G, Centre Hospitalier Lyon-Sud, Pierre-Bénite; Fric D, Clinique du Mail, Grenoble; Froger X, Centre Hospitalier, Chambery; Geoffrois L, Centre Alexis Vautrin, Vandoeuvre-Les-Nancy; Girre V, Institut Curie, Paris; Gisserot O, Hôpital d'Instruction des Armées Ste Anne, Toulon Naval; Guastalla J-P, Centre Léon Bérard, Lyon; Guichard F, Polyclinique Bordeaux Nord, Bordeaux; Guichard P, Centre d'Oncologie Dunkerquois-Généridis, Dunkerque; Haddad-Guichard Z, CH Chalon-sur-Saône; Hardy-Bessard A-C, Clinique Armoricaine de Radiologie, Saint-Brieuc; Hasbini, A, Clinique Armoricaine de Radiologie, Saint-Brieuc; Hu L, Hôpital Hôtel-Dieu, Paris; Jaubert D, Clinique Tivoli, Bordeaux; Kaminsky MC, Centre Alexis Vautrin, Vandoeuvre-Les-Nancy; Kanoui A, Clinique Claude Bernard, Ermont; Largillier R, Centre Antoine Lacassagne, Nice; Levy C, Centre François Baclesse, Caen; Levy E, HEGP, Paris; Lortholary A, Centre Catherine de Sienne, Nantes; Malaurie E, CHIC, Créteil; Mayeur D, Hôpital André Mignot, Le Chesnay; Mechin I, Hôpital de Chambéry, Chambéry; Mercier-Blas A, Clinique Saint-Vincent, Saint-Gregoire; Mignot L, Hôpital Foch, Suresnes; Morvan F, CH René Dubos, Pontoise; Mosser L, Centre Hospitalier, Rodez; Mousseau M, CHU Nord de Grenoble, Grenoble; Peaud PY, Centre Hospitalier, Valence; Platini C, CHR Metz-Thionville, Metz; Provencal J, CH de Annecy, Annecy; Rios M, Centre Alexis Vautrin, Vandoeuvre-Les-Nancy; Rousseau F, CH Pontoise, Pontoise; Serre A, Clinique Rochebelle, Ales; Sillet-Bach I, Centre Hospitalier, Brive; Spaeth D, Centre Alexis Vautrin, Vandoeuvre-Les-Nancy; Thyss A, Centre Antoine Lacassagne, Nice; Tigaud JD, Hôpital Edouard Herriot, Lyon; Walter S, CHR Notre Dame de Bon Secours, Metz; Yakendji K, CHIC, Créteil; Zanetta S, Centre Georges François Leclerc, Dijon; Zylberait D, Centre Hospitalier Général, Compiègne.
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Acknowledgements |
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We thank Christiane Dumont-Puleo for data management. This study was supported by a grant from Schering-Plough, France. Results of this study have previously been presented at the American Society of Clinical Oncology Annual Meeting 2002 (abstract 828) and 2004 (abstract 5022).
Received for publication May 25, 2006. Revision received August 30, 2006. Accepted for publication August 31, 2006.
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References |
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TopAbstractintroductionpatients and methodsresultsdiscussioncontributorsAcknowledgementsReferences |
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1. The ICON and Collaborators AGO. (2003) Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer; the ICON4/AGO-OVAR-2.2 trial. Lancet 361:2099–2106.[CrossRef][Web of Science][Medline]
2. McGuire WP, Hoskins WJ, Brady MF, et al. (1996) Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 334:1–6.
3. Piccart MJ, Bertelsen K, Stuart G, et al. (2003) Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin regimen over the cyclophosphamide-cisplatin combination in advanced ovarian cancer. Int J Gynecol Cancer 13:144–148.
4. Muggia FM, Braly PS, Brady MF, et al. (2000) Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: a gynecologic oncology group study. J Clin Oncol 18:106–115.
5. Neijt JP, Engelholm SA, Tuxen MK, et al. (2000) Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol 18:3084–3092.
6. Greimel ER, Bjelic-Radisic V, Pfisterer J, et al. (2006) Randomized study of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group comparing quality of life in patients with ovarian cancer treated with cisplatin/paclitaxel versus carboplatin/paclitaxel. J Clin Oncol 24:579–586.
7. Bookman MA, Greer BE, Ozols RF. (2003) Optimal therapy of advanced ovarian cancer: carboplatin and paclitaxel vs. cisplatin and paclitaxel (GOG 158) and an update on GOG 0182–ICON5. Int J Gynecol Cancer 6:735–740.
8. Vasey PA, Jayson GC, Gordon A, et al. (2004) Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst 22:1682–91.
9. International Collaborative Ovarian Neoplasm Group. (2002) Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomized trial. Lancet 360:505–515.[CrossRef][Web of Science][Medline]
10. Sandercock J, Parmar MK, Torri V. (1998) First-line chemotherapy for advanced ovarian cancer: paclitaxel, cisplatin and the evidence. Br J Cancer 78:1471–1478.[Web of Science][Medline]
11. Berek JS, Berrelsen K, du Bois A, et al. (1999) Advanced epithelial ovarian cancer: 1998 consensus statements. Ann Oncol 10:Suppl 1, 87–92.
12. Guastalla JP, Pujade-Lauraine E, Weber B, et al. (1998) Efficacy and safety of the paclitaxel and carboplatin combination in patients with previously treated advanced ovarian cancer. A multicenter GINECO phase II study. Ann Oncol 9:37–43.
13. Martin FJ and Gabizon A, et al. (1992) Human pharmacokinetics of stealth liposomes containing doxorubicin. J Cell Biochem 16E:Suppl, 98.
14. Gabizon A, Catane R, Uziely B, et al. (1994) Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer Res 54:987–992.
15. Uziely B, Jeffers S, Isacson R, et al. (1995) Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies. J Clin Oncol 13:71777–1785.
16. Berry G, Billingham M, Alderman E, et al. (1998) The use of cardiac biopsy to demonstrate reduced cardiotoxicity in AIDS Kaposi's sarcoma patients treated with pegylated liposomal doxorubicin. Ann Oncol 9:711–716.
17. O'Byrne KJ, Bliss P, Graham JD, et al. (2002) A phase III study of Doxil/Caelyx versus paclitaxel in platinum-treated, taxane-naive relapsed ovarian cancer. Proc Am Soc Clin Oncol 21:203a (Abstr 808).
18. Gordon AN, Fleagle JT, Guthrie D, et al. (2001) Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus toptecan. J Clin Oncol 19:3312–3322.
19. Gordon AN, Tonda M, Sun S. (2004) Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol 95:7–8 Doxil Study 30-49 Investigators.
20. Calvert AH, Newell DR, Gumbrell LA, et al. (1989) Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 7:1748–1756.[Abstract]
21. Rustin GJ, Nelstrop AE, McClean P, et al. (1996) Defining response of ovarian carcinoma to initial chemotherapy according to serum CA 125. J Clin Oncol 14:1545–1551.
22. Vergote I, Rustin GJS, Eisenhauer EA, et al. (2000) Re: new guidelines to evaluate the response to treatment in solid tumors [ovarian cancer]. J Natl Cancer Inst 92:1534–1535.
23. O'Brien PC and Fleming TR. (1979) A multiple testing procedure for clinical trials. Biometrics 35:549–556.[CrossRef][Web of Science][Medline]
24. Armstrong DK. (2002) Relapsed ovarian cancer: challenges and management strategies for a chronic disease. Oncologist 7:Suppl 5, 20–28.
25. Goncalves A, Braud AC, Viret F, et al. (2003) Phase I study of pegylated liposomal doxorubicin (Caelyx) in combination with carboplatin in patients with advanced solid tumors. Anticancer Res 23:3543–3548.[Web of Science][Medline]
26. du Bois A, Burges A, Meier W, et al. (2006) Pegylated liposomal doxorubicin and carboplatin in advanced gynecologic tumors: a prospective phase I/II study of the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR). Ann Oncol 17:93–96.
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  B. WEBER, A. LORTHOLARY, F. MAYER, H. BOURGEOIS, H. ORFEUVRE, M. COMBE, C. PLATINI, J. CRETIN, D. FRIC, D. PARAISO, et al. Pegylated Liposomal Doxorubicin and Carboplatin in Late-relapsing Ovarian Cancer: A GINECO Group Phase II Trial Anticancer Res, October 1, 2009; 29(10): 4195 - 4200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. McWhinney, R. M. Goldberg, and H. L. McLeod Platinum neurotoxicity pharmacogenetics Mol. Cancer Ther., January 1, 2009; 8(1): 10 - 16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Katsumata, Y. Fujiwara, T. Kamura, T. Nakanishi, M. Hatae, D. Aoki, K. Tanaka, H. Tsuda, S. Kamiura, K. Takehara, et al. Phase II Clinical Trial of Pegylated Liposomal Doxorubicin (JNS002) in Japanese Patients with Mullerian Carcinoma (Epithelial Ovarian Carcinoma, Primary Carcinoma of Fallopian Tube, Peritoneal Carcinoma) Having a Therapeutic History of Platinum-based Chemotherapy: A Phase II Study of the Japanese Gynecologic Oncology Group Jpn. J. Clin. Oncol., November 1, 2008; 38(11): 777 - 785. [Abstract] [Full Text] [PDF]
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