Prospective phase II study of neoadjuvant therapy with cisplatin, 5-fluorouracil, and bevacizumab for locally advanced resectable esophageal cancer.

BACKGROUND: We investigated the efficacy and tolerability of cisplatin and 5-fluorouracil (5-FU) plus bevacizumab as neoadjuvant therapy for patients with locally advanced resectable esophageal cancer. PATIENTS AND METHODS: In this prospective phase II study, 22 patients with adenocarcinoma and 6 with squamous cell carcinoma received 2 4-day cycles of bevacizumab 7.5 mg/kg followed by cisplatin 80 mg/m(2) infusion on day 1 followed by 5-FU 1,000 mg/m(2) as a 96-h continuous infusion on days 1-4, separated by a 3-week interval. RESULTS: The response rate was 39%, the R0 resection rate was 43%, and the median overall survival (OS) was 17 months. The regimen was well tolerated, with the most common severe toxicities being venous thromboembolism (10%), nausea, and gastrointestinal bleeding (7% each). In 37 patients previously treated with cisplatin and 5-FU alone at our institution and thus serving as historical controls, the response rate was 30%, the R0 resection rate was 44%, and the median OS was 23 months. There was no statistically significant difference between the 2 groups of patients. CONCLUSION: Adding bevacizumab to cisplatin and 5-FU neoadjuvant chemotherapy was active and well tolerated but did not seem to improve the resection rate or OS compared with prior regimens, including the historical controls at our institution.

Phase II study of UFT with leucovorin plus hepatic arterial infusion with irinotecan, 5-fluorouracil and leucovorin for non-resectable liver metastases of colorectal cancer.

BACKGROUND: Compared with systemic therapy, hepatic arterial infusion (HAI) increases the response to fluoropyrimidines. METHODS: Thirty-one patients with non-resectable, colorectal cancer (CRC) liver metastases received irinotecan 120 mg/m(2), followed by leucovorin (LV) 20 mg/m(2) and 5-fluorouracil (5-FU) 500 mg/m(2) administered by HAI every 2 weeks, plus UFT (tegafur-uracil) 200 mg/m(2)/day with LV 30 mg/day on days 1-22, followed by a 6-day rest. RESULTS: The objective response rate was 65% (all 20 patients achieving a partial response). Ten patients (32%) had stable disease. The median time to progression (TTP) and overall survival (OS) were 12 and 36 months. OS was similar in patients with low versus high expression of thymidylate synthase (TS) and/or dihydropyrimidine dehydrogenase (DPD). The regimen was well tolerated. CONCLUSIONS: UFT with LV plus HAI irinotecan and 5-FU/LV was a feasible and effective treatment for non-resectable CRC liver metastases, increasing response, TTP and OS. TS and DPD levels in liver metastases did not predict outcome.

Phase II study of cisplatin, epirubicin, UFT, and leucovorin (PELUF) as first-line chemotherapy in metastatic gastric cancer.

More than two-thirds of patients with gastric cancer present with metastatic disease and their curative options are limited. This phase II study assessed the efficacy and tolerability of cisplatin, epirubicin, tegafur-uracil (UFT) and leucovorin in patients with metastatic gastric cancer (MGC). Thirty-nine patients with previously untreated metastatic or unresectable gastric cancer received intravenous cisplatin 60 mg/m2 and epirubicin 50 mg/m2 on day 1 of a 28-day cycle; UFT 300 mg/m2 was administered with oral leucovorin 30 mg/day in divided doses on days 1-22, followed by a 7-day rest. Two patients achieved a complete response, 13 had a partial response (overall response rate 38%; 95% confidence interval [CI] 24-52%) and 16 patients (41%) had stable disease. Median time to progression was 6.5 months (95% CI 5.5-7.5 months); overall survival was 9.5 months (95% CI 8.5-13.5 months). Grade 3/4 neutropenia, anemia, and thrombocytopenia occurred in 20%, 8%, and 3% of patients, respectively; two patients experienced febrile neutropenia. Grade 3 diarrhea occurred in three patients. The combination of cisplatin, epirubicin, UFT, and leucovorin has significant activity and tolerable toxicities in patients with MGC and represents a convenient treatment option for these patients.