This multicentric, randomized, two-stage phase II trial evaluated three simplified weekly infusional regimens of fluorouracil (FU) or FU plus folinic acid (FA) and cisplatin (Cis) with the aim to ...select a regimen for future phase III trials.
A total of 145 patients with advanced gastric cancer where randomly assigned to weekly FU 3,000 mg/m2/24 hours (HD-FU), FU 2,600 mg/m2/24 hours plus dl-FA 500 mg/m2 or l-FA 250 mg/m2 (HD-FU/FA), or FU 2000 mg/m2/24 hours plus FA plus biweekly Cis 50 mg/m2, each administered for 6 weeks with a 1-week rest. The primary end point was the response rate.
Confirmed responses were observed in 6.1% (two of 33) of the eligible patients treated with HD-FU, in 25% (12 of 48, including one complete remission CR) with HD-FU/FA, and in 45.7% (21 of 46, including four CRs) with HD-FU/FA/Cis. The HD-FU arm was closed after stage 1 because the required minimum number of responses was not met. The median progression-free survival of all patients in the HD-FU, HD-FU/FA, and HD-FU/FA/Cis arm was 1.9, 4.0, and 6.1 months, respectively. The median overall survival was 7.1, 8.9, and 9.7 months, and the survival rate at 1 year was 24.3%, 30.3%, and 45.3%, respectively. Grade 4 toxicities were rare. The most relevant grade 3/4 toxicities were neutropenia in 1.9%, 5.4%, and 19.6%, and diarrhea in 2.7%, 1.9%, and 3.9% of the cycles in the HD-FU, HD-FU/FA, and HD-/FU/Cis arms, respectively.
Weekly infusional FU/FA plus biweekly Cis is effective and safe in patients with gastric cancer.
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Background
Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400mg/day (n=400) could be optimized by doubling the dose (n=420), adding IFN ...(n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128).
Methods
From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. The impact of patients' and disease factors on survival was prospectively analyzed. At the time of evaluation, at least 62% of patients still received imatinib, 26.2% were switched to 2nd generation tyrosine kinase inhibitors.
Results
After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival 80% and 10-year relative survival 92%. In spite of a faster response with IM800mg, the survival difference between IM400mg and IM800mg was only 3% at 5 years. In a multivariate analysis, the influence on survival of risk-group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs. other) was significant in contrast to any form of initial treatment optimization. Patients that reached the response milestones 3, 6 and 12 months, had a significant survival advantage of about 6% after 10 years regardless of therapy. The progression probability to blast crisis was 5.8%. Blast crisis was proceeded by high-risk additional chromosomal aberrations.
Conclusions
For responders, monotherapy with IM400mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease and blast crisis, more life-time can currently be gained by carefully addressing non-CML determinants of survival.
Hehlmann:Novartis: Research Funding; BMS: Consultancy. Saussele:Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Pfirrmann:BMS: Honoraria; Novartis: Honoraria. Krause:Novartis: Honoraria. Baerlocher:Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria. Bruemmendorf:Novartis: Research Funding. Müller:Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Ariad: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Jeromin:MLL Munich Leukemia Laboratory: Employment. Hänel:Roche: Honoraria; Novartis: Honoraria. Burchert:BMS: Honoraria. Waller:Mylan: Consultancy, Honoraria. Mayer:Eisai: Research Funding; Novartis: Research Funding. Link:Novartis: Honoraria. Scheid:Novartis: Honoraria. Schafhausen:Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Ariad: Honoraria. Hochhaus:Incyte: Research Funding; MSD: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; BMS: Research Funding; ARIAD: Research Funding.
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