Bimonthly Chemotherapy with Oxaliplatin, Irinotecan, Infusional 5-Fluorouracil/Folinic Acid in Patients with Metastatic Colorectal Cancer Pretreated with Irinotecan- or Oxaliplatin-Based Chemotherapy

• Published in: Journal of chemotherapy (Florence) 2008-10, Vol.20 (5), p.622-631
• Main Authors: Nobili, S., Checcacci, D., Filippelli, F., Del Buono, S., Mazzocchi, V., Mazzei, T., Mini, E.
• Format: Article
• Language: English
• Subjects: 5-fluorouracil; Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adult; Aged; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Camptothecin - administration & dosage; Camptothecin - adverse effects; Camptothecin - analogs & derivatives; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; combination chemotherapy; Drug Resistance, Neoplasm - drug effects; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Gastroenterology. Liver. Pancreas. Abdomen; Humans; irinotecan; Kaplan-Meier Estimate; Leucovorin - administration & dosage; Leucovorin - adverse effects; Male; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; oxaliplatin; Pharmacology. Drug treatments; Salvage Therapy - methods; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 1120-009X; 1973-9478
• DOI: 10.1179/joc.2008.20.5.622

This study was conducted to assess the tolerability and efficacy of a ternary bi-monthly irinotecan (CPT-11) - oxaliplatin (OHP) - infusional 5-fluorouracil (5-FU)/folinic acid (FA) combination in advanced colorectal cancer patients who had received prior CPT-11 and/or OHP-based chemotherapy regimen. Colorectal cancer patients were given bimonthly CPT-11 as a 90-min infusion, followed by OHP (85 mg/m 2 ), FA (200 mg/m 2 ) 2-h infusions and 5-FU (48-h infusion). CPT-11 and 5-FU doses were escalated as reported below. 26 patients were recruited. Fourteen patients had received a prior CPT-11-, 6 patients a prior OHP-based chemotherapy regimen and 6 patients both regimens. Three dose levels were investigated: CPT-11 100, 120 and 140 mg/m 2 and 5-FU 1500, 1800 and 2100 mg/m 2 in 6, 12 and 8 patients, respectively. All patients were evaluable for toxicity, 24 for antitumor activity. At all dose levels toxicity was ac-ceptable. Grade 4 toxicity occurred in two patients only (neutropenia in one case and stomatitis in another one, 3.8%). Grade 3 toxicities included nausea and vomiting (34.6%), asthenia (26.9%), neurosensory toxicity (15.4%), neutropenia (3.8%) and di-arrhea (3.8%). Hematological toxicity was infrequent and generally mild. At the third dose level, a higher, although not significantly different incidence of hematological and neurosensory toxicity (both occurring in 62.5% of cases, all grades) was observed compared to the other two, while nausea and vomiting were significantly less frequent (37.5% vs 100%). Overall, we observed 2 complete responses, 9 partial responses (OR 45.8%), 8 stable disease (33.3%), and 5 disease progression (20.8%). Median overall survival was 18 months and median time-to-progression 5.5 months. This combination showed moderate toxicity and promising antitumor activity in CPT-11 and/or OHP pretreated colorectal cancer patients. The second dose level using CPT-11 at 120 mg/m 2 and 5-FU at 1800 mg/m 2 is recommended for further phase II studies in this patient population.