[Show abstract][Hide abstract] ABSTRACT: The combination of a fixed dose rate (FDR) infusion of gemcitabine and irinotecan may have a synergistic effect in the treatment of patients with advanced and metastatic pancreatic and biliary cancer. The current study was conducted to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of the combination.
There were 32 patients with metastatic pancreatic and advanced unresectable/metastatic biliary adenocarcinoma who were entered into this open-label, phase 1 dose escalation trial. Gemcitabine was administered at an FDR of 10 mg/m(2)/minute intravenously (iv). Irinotecan was administered iv over 60 minutes after gemcitabine. Both gemcitabine and irinotecan were given on Days 1 and 8 of a 21-day cycle.
The MTD of the combination was gemcitabine at an FDR of 1200 mg/m(2) and irinotecan at a dose of 100 mg/m(2). The DLTs were neutropenia and neutropenic fever. Other DLTs included diarrhea, dehydration, and fatigue. Two patients developed deep venous thrombosis during the treatment. The efficacy of the combination was encouraging, even at the lower dose levels. Of 30 assessable patients, there was 1 complete response, 6 partial responses, and 16 patients with stable disease, with a response rate of 23%, a disease control rate of 76%, a median progression-free survival of 4.7 months, and a median overall survival of 7.0 months. The average number of treatment cycles received was 11.
The recommended doses of the combination for future study are gemcitabine at an FDR of 1200 mg/m(2) and irinotecan at a dose of 100 mg/m(2). The efficacy of the combination is encouraging. Further assessment of the combination with or without biologic agents is suggested.
Cancer 01/2008; 110(12):2768-74. · 5.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hypersensitivity reactions to cisplatin and carboplatin have been reported in the literature to occur at a rate of 10%-27%. Initial reports of hypersensitivity reactions to oxaliplatin were low; however, more recently, it appears as if the incidence of hypersensitivity reactions to oxaliplatin is similar to that of the earlier generation platinum agents. The degree of the reaction varies from mild flushing to life-threatening anaphylactic responses. After a mild hypersensitivity reaction to oxaliplatin, re-exposing a patient can be considered after administering immunosuppressants (eg, high-dose corticosteroids and histamine antagonists) and/or prolonging the duration of oxaliplatin infusion. In the case of moderate-to-severe reactions to oxaliplatin, re-exposure is usually not considered, and alternative forms of therapy should be explored. However, there are reports of successful desensitization to oxaliplatin, and therefore, re-exposing a patient can be considered after carefully weighing the risks and benefits of additional oxaliplatin therapy.
Clinical Colorectal Cancer 08/2006; 6(2):114-7. · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The treatment of metastatic pancreatic cancer continues to be a major unresolved health problem and a therapeutic challenge, with a poor median survival averaging 3-6 months. Disappointing response rates to standard single-agent therapy have led to a search for more effective agents. Early study results with gemcitabine indicate a potential survival benefit in these patients, which is illustrated here in a case report of a 75-year-old man with metastatic pancreatic adenocarcinoma who has defied the odds. Chemotherapy with GEMOX (gemcitabine and oxaliplatin) was initiated, and the patient has enjoyed a good quality of life, with long-term disease control (stable disease 21 months after diagnosis).