Oxaliplatin plus 5-fluorouracil/folinic acid as palliative treatment for progressive malignant gastrointestinal neuroendocrine carcinomas

Abstract

14074 Background: Oxaliplatin in combination with 5-fluorouracil and folinic acid is an antitumoral agent with relatively low toxicity and satisfactory efficacy in several gastrointestinal neoplasms. However, it has not been studied in malignant gastrointestinal neuroendocrine carcinomas (NEC) for which platinum-based chemotherapy is a standard treatment with considerable toxicity. Methods: 16 patients (6 female, 10 male; mean age 57) with documented progress of histologically proven, irresectable, malignant NEC were retrospectively analyzed for safety and efficacy of cytotoxic treatment (from october 2001 to december 2005) according to the FOLFOX-4 regimen. Primary tumors were in the foregut in 9 (2 bronchial, 5 pancreas, 2 stomach), in the midgut in 3 (1 ileum, 2 coecum), and in the hindgut in 2 (1 colon, 1 rectum) patients. The primary tumor was unknown in 2 patients. No patient had clinical signs of hormone hypersecretion. NEC were low-grade malignant in 8 and high grade malignant in the remaining 8 cases. The ki67-index was ≥ 10% in 13 cases (81.3%). Results: A mean of 7.25 cycles (range 1–19) of FOLFOX-4 were administered. Stable disease for a minimum of 9 weeks was observed in 62.5% (10/16) for a mean duration of 19.4 weeks; overall mean time to progression (TTP) as measured by imaging studies was 17.8 weeks (range 2–70 weeks). Reasons for discontinuation of treatment included documented tumor progression in 8 cases (50%) and adverse events in 4 cases (25%) (grade II neurotoxicitiy in 3 cases and grade III neutropenia in 2 cases). 2 patients died during treatment due to tumor progression. 4 patients currently still receive FOLFOX-4 after a mean treatment period of 16 weeks. Side effects according to CTC-NCI-criteria include mild anemia (grade I: n=15), thrombocytopenia (I: n=4, II: n=1), neutropenia (I: n=1, III: n=2), increased serum creatinine (I: n=2), nausea (I: n=4, II: n=4, III: n=1), vomiting (I: n=2, II: n=2), and neurotoxicity (I: n=1, II: n=4). Conclusions: The FOLFOX-4 regimen was well tolerated and effective in progressive malignant NEC with increased proliferative potential. Response may be comparable to current standard regimens. FOLFOX-4 should be evaluated in a prospective controlled clinical trial. No significant financial relationships to disclose.