Efficacy and tolerability of oxaliplatin plus irinotecan 5-fluouracil and leucovorin regimen in advanced stage colorectal cancer patients pretreated with irinotecan 5-fluouracil and leucovorin.

OBJECTIVES: Oxaliplatin has been introduced in the treatment of advanced colorectal cancer during the past few years. The pre-existing treatment of leucovorin-5-fluorouracil-irinotecan (IFL), although reasonably effective, has needed novel, active agents to increase the response rate and overall survival. We planned this phase 2 study in patients pretreated with IFL, adding oxaliplatin as second-line treatment: our objectives were to determine response rate and overall survival. METHODS: All patients (median age 65) were designated to receive 6 cycles of chemotherapy: leucovorin 200 mg/m2 infused for 60 minutes, 5-fluorouracil 500 mg/m2 bolus at 30 minutes from the start of the previous infusion, irinotecan 135 mg/m2 infused for 90 minutes, and oxaliplatin 135 mg/m2 for 90 minutes, infused sequentially on day 1 and repeated every 3 weeks. Standard ondansetron antiemetic treatment and dexamethasone 8 mg were administered to all patients. No prophylactic recombinant human granulocyte colony-stimulating factor was permitted. RESULTS: Fifty-seven patients were recruited and 54 were evaluable for response, survival, and toxicity. All patients had advanced, inoperable, metastatic disease in the liver and/or lungs, abdominal cavity, and multiple sites. All patients had undergone IFL pretreatment and had no response; 40 had disease progression and 14 had stable disease when entering the present study; 302 chemotherapy cycles (mean 5.92) were administered. There was no treatment delay caused by toxicity (either neutropenia or diarrhea). Irinotecan and oxaliplatin were reduced by 25% in 6 (11.1%) patients. No complete responses were observed; 21 (38.9%) patients achieved partial response, 26 (48.2%) had stable disease, and 7 (13%) had disease progression. Median duration of response was 6 months, time to tumor progression (TTP) 8 months, and median overall survival after the initiation of second-line treatment was 10 months (95% confidence interval [CI], 7.5-12.6). CONCLUSION: The addition of oxaliplatin to IFL as second-line treatment rendered a prolongation of survival and a response rate of 38.9% in patients in whom IFL pretreatment had failed.

Therapeutic administration of pegfilgrastim instead of prophylactic use.

OBJECTIVES: Pegfilgrastim is a new growth factor which can be administered subcutaneously once (versus multiple doses for days) on the day neutropenia occurs after chemotherapy. Our aims were to determine: (a) the percentage of patients who needed growth factor (pegfilgrastim) supportive treatment, (b) the duration of neutropenia-leukopenia after pegfilgrastim administration, and (c) the safety in using pegfilgrastim as a treatment and not as a prophylactic agent. MATERIALS AND METHODS: Ninety-eight patients were evaluated. All patients were scheduled to undergo chemotherapy treatment, which was either first- or second-line, and some patients had previously received granulocyte colony-stimulating growth factor (G-CSF): filgrastim on a daily basis. Twenty-five/98 patients required G-CSF support and were treated with pegfilgrastim 6 mg; the first 12 patients were admitted to hospital and remained until recovery from grade 3-4 neutropenia; the other 13 patients were treated on an outpatient basis or at home. Pegfilgrastim was administered when neutropenia appeared (days 6-8 following chemotherapy treatment). RESULTS: Therapeutic administration of pegfilgrastim on the day serious neutropenia occurred was needed by 25/98 patients (25.51%). White blood cell recovery for both grade 3-4 neutropenia was observed within 1-3 days in 75% of the patients treated with pegfilgrastim and in the remaining 25%, within 5 days. CONCLUSION: Pegfilgrastim, an active hemopoietic growth factor with effective slow-absorption properties, can be used safely, not necessarily as a prophylactic agent but on an outpatient basis as a therapy for serious neutropenia.

Long-term survival of patients with advanced colorectal cancer may not be due to the response to chemotherapy.

Our primary objective was to determine the median and overall survival and secondarily the response rate to first- and second-line chemotherapy of patients with advanced colorectal metastatic disease. Three-hundred and seventy-nine patients (median age 60 years, range 30-87 years) were enrolled from April 1993 to March 2000. Median follow-up was 6 years (range 3-10 years), until July 2003. All patients were evaluable for survival and 342 were evaluable for response and toxicity. Thirty-seven patients did not undergo chemotherapy. All patients had confirmed histology as well as metastatic disease based on radiological tests. First-line treatment was administered to 342 patients: leucovorin (LV) 30 mg/m2 and 5-fluorouracil (5-FU) 425 mg/m2. Three different combinations were given as second-line treatment during different chronological periods: i) 5-FU, mitomycin-C and doxorubicin (FAM); ii) 5-FU and cisplatin (CDDP) and iii) 5-FU, LV and irinotecan (CPT-II). Responses were observed as follows: first-line treatment 16.37%, after FAM 25%, following 5-FU-CDDP 26.83% and after 5-FU-LV-CPT-II, 30.61%. Survival of all patients was as follows: median 25 months (range 16.1-33.9 months). The longest survival was of patients on 5-FU-LV-CPT-II. Median survival of patients with stable disease was 19 months and of untreated patients 12 months. Patients with advanced colorectal cancer have a long median (25 months) and overall survival, despite low responsiveness to chemotherapy.