bay-12-9566 and Pancreatic-Neoplasms

The prognosis of pancreatic cancer is poor at any stage. The complete resection of the tumour offers the only chance of cure, but 10-25 % of the patients at most present with operable disease, and median survival following surgery with curative intention is 18 months. Local recurrence is often accompanied or rapidly followed by distant metastasis. Studies of postoperative (adjuvant) treatment have yielded contradictory results. Combined radiochemotherapy resulted in improved survival in a few studies while others failed to demonstrate any survival benefit. Intraoperative radiation therapy given in addition to percutaneous irradiation may improve local tumour control at best. At present only few data support the benefit of adjuvant systemic chemotherapy alone. Unfortunately, the recently completed ESPAC-1 study was not very helpful in settling this issue due to its problematic design. Therefore, the results of ongoing studies of adjuvant chemotherapy are eagerly awaited. These studies have also included arms with gemcitabine, the current standard for palliative treatment of pancreatic cancer, and will hopefully allow firm conclusions as to the role of postoperative chemotherapy.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biphenyl Compounds; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Deoxycytidine; Fluorouracil; Gemcitabine; Humans; Intraoperative Care; Metalloendopeptidases; Neoplasm Metastasis; Neoplasm Recurrence, Local; Organic Chemicals; Palliative Care; Pancreatectomy; Pancreatic Neoplasms; Phenylbutyrates; Postoperative Care; Prognosis; Radiotherapy Dosage; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Time Factors

In view of the data available from randomized trials, gemcitabine has been established as a new standard for the treatment of pancreatic cancer. It was shown to improve clinical benefit response, time to progression, and survival when compared with agents such as 5-fluorouracil or metalloproteinase inhibitors. In one trial, the combination of cisplatin and gemcitabine significantly improved tumor response and time to progression as compared with gemcitabine alone, while a significant impact on survival yet needs to be shown. No significant, clinically meaningful survival benefit was observed when gemcitabine was combined with bolus or infusional 5-fluorouracil, capecitabine, metalloproteinase inhibitors, or the FTI tipifarnib. Numerous ongoing randomized trials are presently investigating gemcitabine-based combination regimens involving such agents as cisplatin, oxaliplatin, irinotecan, docetaxel, 5-fluorouracil, capecitabine, or pemetrexed.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biphenyl Compounds; Camptothecin; Capecitabine; Cisplatin; Deoxycytidine; Docetaxel; Fluorouracil; Gemcitabine; Glutamates; Guanine; Humans; Hydroxamic Acids; Irinotecan; Organic Chemicals; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Pemetrexed; Phenylbutyrates; Quinolones; Randomized Controlled Trials as Topic; Taxoids

To compare the selective matrix metalloproteinase inhibitor BAY 12-9566 with the nucleoside analog gemcitabine in the treatment of advanced pancreatic cancer.. Patients with advanced pancreatic adenocarcinoma who had not previously received chemotherapy were randomly assigned to receive BAY 12-9566 800 mg orally bid continuously or gemcitabine 1,000 mg/m2 administered intravenously on days 1, 8, 15, 22, 29, 36, and 43 for the first 8 weeks, and then days 1, 8, and 15 of each subsequent 28-day cycle. The primary end point was overall survival; secondary end points were progression-free survival, tumor response, quality of life, and clinical benefit. The planned sample size of the study was 350 patients. Two formal interim analyses were planned.. The study was closed to accrual after the second interim analysis on the basis of the recommendation of the National Cancer Institute of Canada Clinical Trials Group Data Safety Monitoring Committee. There were 277 patients enrolled onto the study, 138 in the BAY 12-9566 arm and 139 in the gemcitabine arm. The rates of serious toxicity were low in both arms. The median survival for the BAY 12-9566 arm and the gemcitabine arm was 3.74 months and 6.59 months, respectively (P <.001; stratified log-rank test). The median progression-free survival for the BAY 12-9566 and gemcitabine arms was 1.68 and 3.5 months, respectively (P <.001). Quality-of-life analysis also favored gemcitabine.. Gemcitabine is significantly superior to BAY 12-9566 in advanced pancreatic cancer.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Biphenyl Compounds; Deoxycytidine; Disease Progression; Female; Gemcitabine; Humans; Male; Neoplasm Metastasis; Organic Chemicals; Pancreatic Neoplasms; Phenylbutyrates; Proportional Hazards Models; Quality of Life; Statistics, Nonparametric; Survival Analysis; Treatment Outcome