Weekly therapy with folinic acid (FA) and high-dose 5-fluorouracil (5-FU) 24-hour infusion in pretreated patients with metastatic colorectal carcinoma

Weh, H. J.; Wilke, H.; Dierlamm, Judith; Klaassen, U.; Siegmund, R.; Illiger, H. J.; Schalhorn, Andreas; Kreuser, E. D.; Hilgenfeld, U.; Steinke, B.; Weber, Walter; Burkhard, Oswald; Zöller, A; Pfitzner, J.; Šubert, R.; Kriebel, Reinholde; Hossfeld, Dieter K.

doi:10.1093/oxfordjournals.annonc.a058799

Cited by 78 publications

(48 citation statements)

References 20 publications

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“…However, 45% of patients revealed disease stabilisation lasting for a median interval of 3.2 months. These data are clearly inferior to other agents such as irinotecan (CPT-11) (Rothenberg et al, 1996;Rougier et al, 1997;Van Cutsem et al, 1999) or oxaliplatin plus 5-FU/folinic acid (de Gramont et al, 1997), and appear equal to infusional 5-FU plus high-dose folinic acid (Ardalan et al, 1991;Weh et al, 1994;Hartmann et al, 1998b) alone. Thus, with currently available treatment options for metastatic colorectal cancer, a clear role for infusional 5-FU/bolus MMC cannot be identified (Hejna et al, 2000;Comella et al, 2001;Sobrero et al, 2001;Scheithauer et al, 2002).…”

Section: Discussionmentioning

confidence: 93%

Protracted infusional 5-fluorouracil plus high-dose folinic acid combined with bolus mitomycin C in patients with gastrointestinal cancer: a phase I/II dose escalation study

et al. 2003

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The aim of this study was to define the maximum tolerated dose (MTD) of bolus mitomycin C (MMC) in combination with 24 hcontinuous infusion of 5-flourouracil (FU) plus folinic acid, and to assess the toxicity and activity in patients with previously treated colorectal and gastric cancer. Escalating doses of MMC starting from 6 mg m À2 in 2 mg m À2 -steps to a maximum of 10 mg m À2 were applied on days 1 and 22, given to fixed doses of 5-FU (2.600 mg m À2 ) as 24 h infusion and folinic acid 500 mg m À2 prior to 5-FU weekly for 6 weeks. At least three patients were treated at each dose level. A total of 16 patients have been included in the phase I study. At the highest dose level (MMC 10 mg m À2 ), grade III thrombocytopenia, dyspnoea, mucositis and diarrhoea were observed in one patient each (17 %). In the phase II study 45 patients, 33 with colorectal cancer and 12 with gastric cancer, 23 patients after failure of first-and 22 patients after at least second-line or subsequent chemotherapy have been treated. Seven partial responses (PR) were registered (16%), one (3%; CI 95% , 0 -16) in colorectal and six (50%; CI 95% , 21 -79%) in gastric cancer patients. In all, 17 (38%) achieved disease stabilisation, 15 colorectal (45%, CI 95% , 28 -64%) and two gastric cancer patients (17%; CI 95% , 2 -48%). The median progression-free survival was 3.1 months (range, 0.9 -9.1) in colorectal and 4.6 months (range, 0.7 -12.4) in gastric cancer. The median overall survival time was 6.6 months (range, 1.9 -15.6) in colorectal and 7.1 months (range, 1.7 -20.8) in patients with gastric cancer. This regimen was considered to be safe and well tolerated for pretreated patients with gastrointestinal adenocarcinoma. In gastric cancer,MMC plus infusional 5-FU/folinic acid may be a potential second-line regimen with promising antitumour activity.

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Section: Discussionmentioning

confidence: 93%

Protracted infusional 5-fluorouracil plus high-dose folinic acid combined with bolus mitomycin C in patients with gastrointestinal cancer: a phase I/II dose escalation study

et al. 2003

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“…It is noteworthy that most of the objective responses observed with 5-FU-based second-line regimens occurred either in patients who had previously responded to 5-FU or in patients who had previously received suboptimal doses of 5-FU. Indeed it appears that previous treatment with 5-FU/LV regimens predicts a poor response to a second 5-FU-based regimen [7].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, most attempts at second-line chemotherapy comprise further 5-FU-modulated treatments. Overall, approximately 10% of patients at most will respond to second-line 5-FU-based chemotherapy, whatever the schedule of 5-FU and/or the modulator agents might be [6,7].…”

Section: Introductionmentioning

confidence: 99%

Clinical activity and benefit of irinotecan (CPT-11) in patients with colorectal cancer truly resistant to 5-fluorouracil (5-FU)

Cutsem¹,

Cunningham

Huinink

et al. 1999

European Journal of Cancer

101

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The aim of this prospective study was to assess the eYcacy, clinical bene®t and safety of in patients with stringently-de®ned 5-¯uorouracil-resistant metastatic colorectal cancer (CRC). 107 patients with documented progression of metastatic CRC during 5-FU were treated with CPT-11 350 mg/m 2 once every 3 weeks in a multicentre phase II study. Tumour response and toxicity were assessed using WHO criteria. Changes in performance status (PS), weight and pain were also measured. The WHO response rate was 13/95 (13.7%, 95% CI 7.5% to 22.3%) eligible patients with a median duration of response of 8.5 months (37 weeks, range: 18±53 +). There was also a high rate of disease stabilisation (44.2%) with a median duration of 4.8 months. The probability of being free of progression at 4 months was 50%. Median survival from ®rst administration of CPT-11 was 10.4 months or 45 weeks (range: 3±66 + weeks). There was weight stabilisation or gain in 81% (73/90) of patients, a favourable outcome in PS in 91% (82/90) (improvement of WHO PS 2 or stabilisation of PS 0-1), and pain relief in 54% (26/48). There were no toxic deaths. Neutropenia was short-lasting and non-cumulative. Diarrhoea grade ! 3 occurred in 7% of cycles and 28/107 (26%) of patients. CPT-11 350 mg/m 2 once every 3 weeks has an encouraging degree of activity in progressive metastatic CRC truly resistant to 5-FU with a relatively high rate of tumour growth control translated into clinical bene®t. The toxicity pro®le of CPT-11 is becoming better understood and has been considerably improved. #

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“…Based on the experience of treating colorectal cancer with chemotherapy, alteration of the 5-FU infusion level may lead to a diVerent toxicity proWle. At least two studies reported mild hematologic and non-hematologic toxicities when 5-FU was used as a 24-h infusion combined with leucovorin (AIO regimen), which may increase both the eYcacy of 5-FU and its toxicity [10,11]. In both studies, less than 10% of patients with colorectal cancer had grade 3-4 mucositis and diarrhea, when they received weekly 5-FU administration.…”

Section: Discussionmentioning

confidence: 99%

“…In studies of nonsmall-cell lung cancer patients, weekly use of docetaxel signiWcantly reduced hematologic toxicity without compromising eYcacy [8,9]. Several studies on colorectal cancer reported low incidences of toxicities for weekly 5-FU administration [10,11]. Based on those results, a weekly DCF (wDCF) regimen is considered optimal for treating metastatic gastric cancer, but a full-scale clinical assessment is needed.…”

Section: Introductionmentioning

confidence: 99%

Phase I dose-escalating study of 24-h continuous infusion of 5-fluorouracil in combination with weekly docetaxel and cisplatin in patients with advanced gastric cancer

Wang

Zhang

Hong

et al. 2008

Cancer Chemother Pharmacol

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Purpose To determine the maximum-tolerated dose (MTD) of a 24-h continuous infusion of 5-Xuorouracil (5-FU) when administered in combination with a Wxed weekly dose of docetaxel and cisplatin in patients with advanced gastric cancer. Methods Patients with advanced gastric adenocarcinoma (n = 21) received a weekly regimen of docetaxel, cisplatin and 5-FU (DCF) for 3 consecutive weeks every 4 weeks. The doses of docetaxel and cisplatin were Wxed at 33.3 and 30 mg/m 2 , respectively. The dose of 5-FU was increased from a starting dose of 1,000 mg/m 2 to the MTD. Results A total of 53 cycles of chemotherapy were administered (median = 3 cycles/patient). The MTD of 5-FU was 1,750 mg/m 2 . All 21 patients were assessed for toxicity and 19 patients (90%) were evaluated for response. Both grade 3-4 hematologic and non-hematologic toxicities occurred in less than 10% of patients and there were no treatment-related deaths. Among the 19 patients, we observed 1 complete and 4 partial responses for an overall response rate of 26% (95% CI: 6-46%). This rate increased to 39% (95% CI: 12-66%) in 13 chemotherapy-naïve patients.Conclusions A consecutive weekly DCF regimen at 4-week intervals appears feasible for advanced gastric cancer with a favorable toxicity proWle. The recommended doses are 33.3 mg/m 2 of docetaxel, 30 mg/m 2 of cisplatin and 1,500 mg/m 2 of a 24-h continuous intravenous infusion of 5-FU. The response of this weekly regimen in our study was favorable and deserved further investigation in a phase II trial.

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Weekly therapy with folinic acid (FA) and high-dose 5-fluorouracil (5-FU) 24-hour infusion in pretreated patients with metastatic colorectal carcinoma

Abstract: Pretreated patients with metastatic colorectal carcinoma, notably those with a primary PR or SD, can probably benefit from weekly high-dose 5-FU/FA.

Cited by 78 publications

References 20 publications

Protracted infusional 5-fluorouracil plus high-dose folinic acid combined with bolus mitomycin C in patients with gastrointestinal cancer: a phase I/II dose escalation study

Protracted infusional 5-fluorouracil plus high-dose folinic acid combined with bolus mitomycin C in patients with gastrointestinal cancer: a phase I/II dose escalation study

Clinical activity and benefit of irinotecan (CPT-11) in patients with colorectal cancer truly resistant to 5-fluorouracil (5-FU)

Phase I dose-escalating study of 24-h continuous infusion of 5-fluorouracil in combination with weekly docetaxel and cisplatin in patients with advanced gastric cancer

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