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The purpose of the study was to assess the efficacy and safety of biweekly oxaliplatin in combination with leucovorin (LV)-modulated bolus plus infusion of 5-fluorouracil (5-FU) in patients with relapsed or metastatic colorectal cancer (CRC) as a second line therapy.
Between November 2002 and October 2005, 26 patients with histologically confirmed relapsed or metastatic CRC were enrolled. All patients were previously treated with irinotecan-based combination chemotherapy. The chemotherapy regimen consisted of oxaliplatin 85 mg/m2 on day 1; LV 200 mg/m2 on days 1 and 2; and 5-FU 400 mg/m2 bolus IV with 600 mg/m2 with a 22-hour infusion on days 1 and 2 every 2 weeks.
The median age of the 26 patients was 50.5 years (range, 31~72). Their metastatic sites included: the liver (42.3%), peritoneum (26.9%), lung (23.1%) and ovary (7.7%). Twenty five patients were evaluated for their response. Four patients achieved partial responses and 15 patients had stable disease. The overall response rate was 16% (95% confidence interval; 1.7~30.3%). The median follow-up duration for the surviving patients was 7.4 months (range, 2.08~21.2). Median overall survival (OS) and 1-year OS rates were 16.7 months and 63.9%, respectively. The most common hematological toxicities were: NCI grade I/II leucopenia (49.3%), grade I/II neutropenia (41%) and grade I/II anemia (65.2%). The main non-hematological toxicities were: grade I/II peripheral neuropathy (16.1% and 21.5%, respectively) and nausea/vomiting (23.6%/18.5%). There was no life-threatening toxicity.
The oxaliplatin, 5-FU and LV combination chemotherapy, scheduled as a biweekly protocol, was effective and well tolerated in the treatment of relapsed or metastatic colorectal cancer patients as second line chemotherapy.
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We prospectively conducted a non-randomized phase II trial to evaluate the efficacy and safety of combination irinotecan, leucovorin (LV) and 5-fluorouracil (FU) as a first-line regimen for treating patients with previously untreated advanced colorectal cancer (CRC).
Twenty-six previously untreated patients with advanced, recurrent or metastatic CRC were enrolled in this study. The patients received either irinotecan 180 mg/m2 on day 1 with LV bolus of 200 mg/m2 and FU bolus of 400 mg/m2, and this was followed by FU continuous infusion of 600 mg/m2 on day 1 and day 2 (the FOLFIRI regimen), or they were treated with LV bolus of 400 mg/m2 and FU bolus of 400 mg/m2 followed by FU continuous infusion of 2,400 mg/m2 for 46 hours (the simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks until disease progression.
The objective response rate was 23.1% (6/26) respectively, for both treatments. The median time to progression was 5.3 months (range: 0.4~19.9), and the overall survival was 11.2 months (range: 0.5~52.3). The prognostic factor for longer survival was the Eastern Cooperative Oncology Group (ECOG) performance status (PS). The non-hematological toxicities were similar for both treatment groups, with more frequent grade ≥3 neutropenia being noted for the simplified FOLFIRI regimen.
The biweekly irinotecan based regimen was demonstrated to have a moderate antitumor activity with acceptable toxicity profiles, and the ECOG PS was the independent prognostic factor.
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The aim of this study was to evaluate the efficacy and tolerability of the oxaliplatin, 5-fluorouracil (5-FU) and low dose leucovorin (LV) combination in patients with advanced colorectal cancer.
Patients with unresectable or recurrent colorectal carcinomas were prospectively accrued. Up to one prior chemotherapy regimen was allowed. Patients received oxaliplatin, 85 mg/m2, administered as a 2-hour infusion on day 1, followed by LV, 20 mg/m2, as a bolus and 5-FU, 1,500 mg/m2, via continuous infusion for 24 hours on days 1 and 2. Treatment was repeated every 2 weeks until disease progression or adverse effects prohibited further therapy.
Between August 1999 and May 2004, 31 patients were enrolled in this study. Of the patients enrolled, 24 and 31 were evaluable for tumor response and survival analysis, respectively. The patients' characteristics included a median age of 59, with 6 (19%) having had prior chemotherapy. No patient achieved a complete response, but nine (38%) attained a partial response. Seven (29%) patients maintained a stable disease and 8 (33%) experienced increasing disease. The median duration of the response was 6 months. After a median follow-up of 9.6 months, the median time to progression was 3.8 months, with a median survival of 10.7 months. The hematological toxicities were mild to moderate, with no treatment-related mortality or infection. The major non-hematological toxicity was gastrointestinal toxicity.
The combination chemotherapy of oxaliplatin, low dose LV and continuous infusion of 5-FU is safe and has a cost-benefit, but is a moderately effective regimen in advanced colorectal cancer. A randomized trial comparing low and high dosages of leucovorin in the FOLFOX regimen is warranted.
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A 13 year-old girl with osteosarcoma and pulmonary tumor recurrence developed acute renal failure following high dose methotrexate (12 g/m2) therapy, she had previously tolerated high dose methotrexate and her renal and hepatic functions were normal. Briefly, 48 hours after beginning methotrexate infusion her methotrexate concentration and creatinine level were 1338.8 µM/L and 5.8 mg/dl, respectively. Grade IV oral mucositis and neutropenia with fever developed at 144 hours after MTX infusion. Hydration and alkalinization were continued and leucovorin rescue was intensified based on the plasma MTX concentrations. Plasma exchange was performed twice and hemodialysis 3 times without problems, but methotraxate and creatinine levels remained high, 91.9 µM/L, and 2.5 mg/dl, respectively. After 3 courses of hemodialysis carboxypeptidase-G2 (CPDG2) was administered at 50 U/kg, intravenously over 5 minutes. After 15 minutes of CPDG2 (Voraxaze™) infusion, her plasma MTX concentration was 0.91 µM/L and no rebound elevation or side effects developed. Thirteen days post-MTX infusion her renal function had normalized. We report here our experience of a dramatic methotrexate level reduction caused by CPDG2 administration.
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The purpose of this study was to assess the efficacy and toxicity of biweekly irinotecan plus 5-fluorouracil (FU) and leucovorin (LV) in patients with relapsed or metastatic colorectal cancer.
Between March 2002 and May 2004, 24 patients with histologically confirmed relapsed or metastatic colorectal cancer were enrolled in this study. One chemotherapy cycle consisted of irinotecan 180 mg/m2 on days 1 and 15; 5-FU 400 mg/m2 bolus IV with 600 mg/m2 by a 22 hour intravenous infusion on days 1, 2, 15 and 16; and leucovorin 20 mg/m2 on days 1, 2, 15 and 16, every 4 weeks.
The median age of the 24 was 57.5 years (range, 38~69). Their metastatic sites included: the liver (62.5%), lung (20.8%), peritoneum (16.7%), lymph node (12.5%), ovary (8.3%) and pelvis/vagina (8.3%). Twenty-two patients were evaluable for a response. Six and 7 patients achieved partial responses and stable diseases, respectively. The overall response rate was 27.3% (95% Confidence interval; 10.3~44.5%). The median follow-up duration for surviving patients was 14.7 months (range, 1.7~26.5). Median overall survival (OS) and 1-year OS rates were 19 months and 86.3%, respectively. Median response duration and median progression free survival were 7.47 and 5.57 months, respectively. A total of 83 cycles (median 4 cycles) were administered. The main non-hematologic toxicities were nausea/vomiting (44.5%/18.1%) and diarrhea (8.4%). The most common hematologic toxicity was NCI grade I/II anemia (31.3%) and grade I/II neutropenia was 10.8%. There was no life-threatening toxicity.
The results suggested that irinotecan, 5-FU and leucovorin combination chemotherapy in a biweekly schedule is a practical and tolerable treatment option in patients with advanced colorectal cancer.
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To determine the efficacy and tolerability of a modified chronomodulated infusion of oxaliplatin, 5-fluorouracil (5-FU) and leucovorin in the treatment of advanced colorectal cancer.
Sixteen patients with relapsed or metastatic colorectal cancer were treated with an intravenous infusion of oxaliplatin 25 mg/m2, 5-FU 700 mg/m2 and leucovorin 20 mg/m2 on days 1 to 5. The infusion of oxaliplatin was chronomodulated with a peak delivery rate at 16:00 p.m., with 5-FU infused constantly overnight. Each course was repeated every 21 days.
The response rate was 38.5% (95% confidence interval [CI], 13.9% to 68.4%) in the 13 measurable patients, including 1 complete response (7.7%) and 4 partial responses (30.8%). Five patients (38.5%) had a stable disease and 3 (23.0%) a progressive disease. Three patients without a measurable lesion had improved status. The median time to progression and overall survival were 29 weeks and 85 weeks, respectively. Grade 3 thrombocytopenia occurred in 2.5% (2 cycles) and grade 3 vomiting in 12.5% (2 patients). Anorexia, stomatitis, diarrhea, pruritus, alopecia and peripheral neuropathy were mild and tolerable.
The modified chronomodulated infusion of oxaliplatin, 5-FU and leucovorin is effective and tolerable, but the number of patients was too small. Further study will be needed to confirm the efficacy of this regimen with a larger population of patients.
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The combination of cisplatin, epirubicin, leucovorin and 5-fluorouracil (PELF) administration, as adjuvant chemotherapy after curative resection for gastirc cancer, was compared with 5-fluorouracil (5-FU) administration alone. This paper reports the results of a prospective randomized comparison of the two regimens, PELF and 5-FU.
From August 1996 to July 1999, 54 patients were selected subsequent to being diagnosed with stage III cancer after a curative resection for gastric cancer. The patients were stratified according to stage IIIA/IIIB and subtotal/total gastrectomy, and then they were randomized into each treatment group, i.e. the PELF or 5-FU alone groups.
54 assessable patients were enrolled in this study: 28 received PELF and 26 received 5-FU alone. 12 patients relapsed in each group and the median follow-up duration was 42 months (range: 10~77 months). The overall survival rate and disease-free survival rate (DFS) were not significantly different between two groups, (5-year survival of PELF vs. 5-FU: 57% vs. 64%, 5-year DFS: 54% vs. 51%). The PELF combination was more toxic in terms of anemia, anorexia, nausea and diarrhea than the 5-FU.
This study showed that the PELF combination, as an adjuvant therapy for gastric cancer after a curative resection, was a less effective treatment, and it had more toxic effects than the 5-FU.
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To determine the activity and toxicities of low dose leucovorin (LV) plus fluorouracil (5-FU) regimen, combined with oxaliplatin every two weeks (modified FOLFOX 4), as a first-line therapy for patients with metastatic colorectal cancer.
Between March 2001 and August 2003, fifty-five patients were enrolled in this study. Patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion at days 1 plus LV 20 mg/m2 over 10 minutes, followed by 5-FU bolusa 400 mg/m2 bolus and 22 hour continuous infusion of 600 mg/m2 5-FU at day 1~2. This treatment was repeated in 2 week intervals.
The objective response rate was 40% on an intent-to-treatment analysis. Three patients (6%) demonstrated a complete response and nineteen patients (38%) showeda partial response. Sixteen patients (32%) showed a stable disease and eleven patients (22%) progressed during the course of the treatment. The median time to progression and overall survival time wereas 6.6 months (95% CI: 4.98~8.02 months) and the median overall survival time was 17.0 months (95% CI: 9.15~24.85 months) from the start of the chemotherapy, respectively. A total of 275 cycles were analyzed for toxicity. Major hematologic toxicities included grade 1~2 anemia (23.5%), neutropenia (25.3%) and thrombocytopenia (10.6%). There were only 2 cycles of neutropenic fever. The most common non-hematologic toxicities were grade 1~2 nausea/vomiting (10.9%), diarrhea (9.1%) and grade 1 neuropathy (18.0%). There was no treatment related death.
The modified folfox 4 regimen is safe and effective regimen as a first-line therapy in advanced colorectal cancer patients.
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