A Phase II Study of Irinotecan Alternated with a Weekly Schedule of Oxaliplatin, High-Dose Leucovorin and 48-Hour Infusion 5-Fluorouracil in Patients with Advanced Colorectal Cancer

Abstract

Objectives: To evaluate the safety and efficacy of irinotecan (CPT-11) alternated with a weekly treatment for 4 weeks of oxaliplatin (L-OHP), high-dose leucovorin (LV) and a 48-hour 5-fluorouracil infusion (5-FU_48h) as first-line chemotherapy for patients with advanced colorectal cancer (ACC). Patients and Methods: Previously untreated patients with ACC received chemotherapy consisting of a weekly treatment for 4 weeks of L-OHP (65 mg/m²), high-dose LV (150 mg/m²) followed by a 5-FU_48h infusion (2,300 or 1,800 mg/m²) alternated with CPT-11 (350 mg/m²). A cycle was to be performed every 8 weeks. Treatment was continued up to tolerance, disease progression or patient refusal. Forty consecutive patients with measurable ACC, aged 26–70, performance status ≤2, entered our study. Results: Six complete and 17 partial responses were observed (overall response rate, 57.5%; 95% confidence interval, CI: 38.8–71.1%); an additional 35% of the patients had stable disease. The median duration of response was 10.9 months (range, 6.5–30+ months). The median time to progression and the median overall survival time were 11.4 (95% CI: 10.4–12.3) and 20.3 (95% CI: 16.4–23.7) months, respectively. At the median follow-up period of 24 months, 17 patients (42.5%) are still alive. After a median number of 4 cycles, one toxic death occurred. The incidence of grade 3–4 toxicity per patient in any cycle was: stomatitis 7.5%, nausea/vomiting 2.5% and diarrhea 45% for the infusional part, neutropenia 37.5%, anemia 2.5%, thrombocytopenia 5%, alopecia 5% and diarrhea 10% for the CPT-11 part of the regimen. Gastrointestinal toxicity was different according to the dose of 5-FU. Serious adverse events occurred most frequently when 5-FU was given at a dose of 2,300 mg/m² with a high incidence of grade 3–4 diarrhea (72.2%) and stomatitis (16.6%), and led to dose reduction of 5-FU in 13 of 18 patients (72.2%). For 22 patients who started 5-FU at a dose of 1,800 mg/m², a dose reduction of 5-FU was necessary only 5 times (22.7%). No patient discontinued treatment because of severe neurotoxicity. Conclusions: The activity of our alternating regimen of L-OHP/LV/5-FU_48h and CPT-11 for not previously treated ACC patients is counterbalanced by a high toxicity and a inconvenient schedule.

Phase II Trial of Oxaliplatin and Tegafur/Uracil and Oral Folinic Acid for Advanced or Metastatic Colorectal Cancer in Elderly Patients

“…We found evidence that our regimen decreases the specific drug neurotoxicity. Possible sources of reduced neurotoxicity include the weekly schedule developed by our group and confirmed by other studies with the same reduced toxicity [16,17,18]and a lower L-OHP dosage for single administration. Only 2 patients experienced grade 3 myelotoxicity.…”

“…After taking into account its reduced neurotoxicity in the weekly schedule [16,17,18],we preferred an L-OHP subdivision dosage at 65 mg/m 2 for single administration. The secondary aims were to evaluate the treatment in terms of time to disease progression (TTP), overall survival (OS), and QoL.…”

Severe Neutropenia is Associated with Better Clinical Outcomes in Patients with Advanced Pancreatic Cancer Who Receive Modified FOLFIRINOX Therapy

“…The occurrence of severe adverse events, including neutropenia [ 11 , 12 ], mucositis [ 13 ], neurotoxicity [ 14 ] and diarrhea [ 15 ], during cancer chemotherapy results in impaired patient quality of life and leads to the therapy interruption or dose reduction. The latter may lead to a reduction in the therapeutic effect due to the decrease in the relative dose intensity (RDI).…”

Evaluation of biodistribution and safety of adenovirus vector containing MDR1 in mice

“…It is sensitive to chemotherapy and possible to be completely remitted remission of it is possible by surgical procedure removal, the prognosis of advanced or relapsed colorectal cancer is not satisfactory[1]. Discovered some 40 years ago, Fluorouracil (FU) is still the most extensively studied drug and is considered to be the standard treatment in colorectal cancer especially in advanced cancer[2]. In recent years, 5-fluorouracil (5-Fu), leucovorin, oxaliplatin and cisplatin combination chemotherapy is one of the most effective regimen in advanced colon cancer[3].…”