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ABSTRACT: Preoperative radiochemotherapy is a cornerstone in patients with non- resectable locally advanced rectal cancer (LARC). To improve outcome (number of R0 resections and survival) high-dose radiotherapy (RT) was combined with oral UFT/l-leucovorin to allow tumour regression before radical intended surgery.
Pelvic RT was delivered with megavoltage photons using a 5 field technique. RT was CT-based, given 5 days a week through one posterior field and two lateral fields (48.6 Gy/27 fractions) to encompass the primary tumour and the regional lymph nodes. In addition, the tumour bed received a concurrent boost (5.4 Gy/27 fractions) and a final boost (6 Gy/3 fractions); thus GTV received 60 Gy/30 fractions. Concurrent with RT patients received a daily dose of oral UFT 300 mg/m(2) plus l-leucovorin 22.5 mg 5/7 days (divided in three doses).
From September 2000 to November 2004, 52 patients (median age 60 years (32-83); median PS 0 (0-2)) with LARC (36 primary, 16 recurrent) were included in this phase II study. All but three patients received the planned 60 Gy, median duration of RT was 42 days (25-49). Toxicity was very modest; only four patients had a dose reduction of UFT. No hematological toxicity of clinical significance was seen. Non-hematological toxicity grade 1 (GI-toxicity, fatigue and/or dysuria) was frequently observed but only four patients experienced grade 3 toxicity (diarrhoea and/or nausea/vomiting). Forty patients (77%) were operated (30 R0, 5 R1, 5 R2) median 55 days (27-112) after completion of RT. Seven (13%) patients had a pathological complete response (pCR). Thirty-one patients (60%) died after median 25.4 months (1.6-45.2 months). Twenty-one patients (40%) are still alive June 2007.
Preoperative high-dose RT and concomitant UFT produces major regression in most patients with non-resectable LARC and thus a good chance of cure.
Acta oncologica (Stockholm, Sweden) 02/2008; 47(3):428-33. · 2.27 Impact Factor
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ABSTRACT: The main objectives of this phase II study were to determine efficacy and safety of the combination of UFT with Leucovorin and mitomycin C in patients with metastatic colorectal cancer. Ninety-seven patients were treated with UFT (91 patients 300 mg/m2, 6 patients 250 mg/m2) + Leucovorin 90 mg days 1-28 q 5 weeks. During the first 4 cycles the patients also received mitomycin C 7 mg/m2 on day 1. At the end of 4 courses patients with benefit from the treatment could receive further courses of UFT and Leucovorin alone. Two patients had a complete response (2%), 20 (21%) had a partial response, 40 (41%) had no change, 19 (20%) had progression, and 16 (17%) were not evaluable for response. The overall response rate by intention to treat was 22/97 (23%). Median time to progression was 5 months and median survival 13 months. Severe (grade 3-4) toxicities included: anorexia 3%, nausea 6%, vomiting 7%, diarrhoea 7%, and fatigue 9%. Febrile neutropenia, renal failure, and thrombocytopenia were seen in 1% of the patients, respectively. The combination of UFT with Leucovorin and mitomycin C shows similar clinical activity with regard to overall response rate (23%) and survival (13 months) to other frontline 5-fluorouracil-based therapies in metastatic colorectal cancer patients. The results indicate that mitomycin C did not increase either efficacy or toxicity. Therefore, phase III trials with this regimen cannot be recommended.
Acta Oncologica 02/2004; 43(3):276-9. · 3.33 Impact Factor
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Acta Oncologica 02/2002; 41(2):202-3. · 3.33 Impact Factor
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Anders Jakobsen,
Ake Berglund,
Bengt Glimelius,
Jan-Erik Frödin, Flemming Hansen,
Mogens Kjaer,
Ebbe Lindegaard Madsen,
Erik Sandberg,
Jan Peter Poulsen,
Göran Carlsson,
Bengt Gustavsson
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ABSTRACT: The effect of different dose intensities of 5-fluorouracil (5-FU) in advanced colorectal cancer was investigated. A total of 312 patients were randomized to receive 400 mg/m2 (group A), 500 mg/m2 (group B) or 600 mg/m2 (group C) of 5-FU with leucovorin 60 mg/m2 on two consecutive days every second week. Treatment continued to progression. Pharmacokinetic analyses with calculation of the area under the concentration (AUC) were performed in 91 patients. The primary endpoint was survival, and secondary endpoints were time to disease progression, toxicity and, if the disease was measurable, tumour response. The study was well balanced in the three groups with respect to a number of patient characteristics. Crude survival as estimated by Kaplan-Meier plots was not statistically significantly different (p = 0.07) but tended to show the best results in the intermediate dose group (median survival 10, 12.5 and 10 months, respectively). Analyses of time to progression or death showed significant differences among the three groups (p = 0.02) with the longest progression-free interval in the intermediate group receiving 500 mg/m2. The objective response rates were 23%, 39% and 28%, respectively (p = 0.02). The actual/projected dose intensity (mg/m2/week) was 92%, 92% and 84%, respectively. AUC did not correlate with response or survival. The frequency of severe side effects in group C was significantly higher than that of groups A and B. The study indicated that an increase from 800 to 1000 mg/m2 of bolus 5-FU fortnightly improved the treatment results but a further increase only worsened the toxicity.
Acta Oncologica 02/2002; 41(6):525-31. · 3.33 Impact Factor
