Annals of Oncology 13:1197-1204, 2002
© 2002 European Society for Medical Oncology
Original Paper |
Whole-body hyperthermia (41.8°C) combined with bimonthly oxaliplatin, high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer: a phase II study
1 Department of Oncology/Hematology, 2 Department of Anesthesiology and 3 Institute of Mathematics and Computer Science in Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany
Received 27 August 2001; revised 17 December 2001; accepted 9 January 2002
Background:
Second- and third-line treatments remain a challenge in advanced colorectal cancer. Studies of bimonthly regimens of high-dose leucovorin (LV) and 5-fluorouracil (5-FU) by continuous infusion combined with oxaliplatin (L-OHP) have shown encouraging response rates in patients not responding to a bimonthly LV/5-FU regimen. Hyperthermic enhancement of L-OHP efficiency by increased DNA adduct formation has been demonstrated in vitro. This study was designed to address feasibility, toxicity and efficacy issues of whole-body hyperthermia (WBH) as an adjunct to L-OHP/LV/5-FU in pretreated patients after progression to first- and second-line treatments with LV/5-FU by continuous infusion and irinotecan.
Patients and methods:
Forty-four patients with advanced colorectal cancer, who had progressed during or within 3 months after completion of chemotherapy with LV/5-FU 24-h infusion (LV/5-FU24h) (eight patients) or irinotecan combined with or after LV/5-FU24h (36 patients), were treated with L-OHP 85 mg/m2, 2-h intravenous (i.v.) infusion, followed by LV 200 mg/m2, 1-h i.v. infusion, and 5-FU 3 g/m2, 48-h continuous infusion. Every second cycle of the biweekly regimen was combined with WBH, thus allowing a comparison of toxicity with and without WBH in the same patient. Whole-body hyperthermia was administered by a humidified radiant heat device. The target temperature of 41.8°C was maintained for 60 min. L-OHP (2-h infusion) was started at a core body temperature of 39°C.
Results:
All patients could be evaluated for toxicity, and 41 patients were evaluable for response. A total of 273 L-OHP-containing regimens were administered, 130 with and 143 without WBH. Hyperthermic treatment combined with L-OHP/LV/5-FU showed no unexpected toxicities. WHO grade 3 toxicities were rare and evenly balanced between cycles given with or without WBH. One early death occurred due to sepsis and tumor lysis. The overall response rate was 20%, with two complete and six partial responses. Twenty-three patients (56%) had stable disease and nine patients (22%) progressive disease. With a median observation time of 70 weeks, the median time to progression was 21 weeks [95% confidence interval (CI) 17–25 weeks] and the median survival was 50 weeks (95% CI 39–61 weeks) from the start of therapy.
Conclusions:
This trial suggests some advantage of combining L-OHP/LV/5-FU with WBH. Results compare favorably with the activity of similar regimens without WBH in less extensively pretreated patients. These data support further evaluation and warrant phase III studies.
Key words: advanced colorectal cancer, 5-fluorouracil, leucovorin, oxaliplatin, whole-body hyperthermia
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  S. Hegewisch-Becker, K. Braun, M. Otte, A. Corovic, D. Atanackovic, A. Nierhaus, D. K. Hossfeld, and K. Pantel Effects of Whole Body Hyperthermia (41.8{degrees}C) on the Frequency of Tumor Cells in the Peripheral Blood of Patients with Advanced Malignancies Clin. Cancer Res., June 1, 2003; 9(6): 2079 - 2084. [Abstract] [Full Text] [PDF]
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