Continuous Infusion High-Dose Leucovorin with 5-Fluorouracil and Cisplatin for Untreated Stage IV Carcinoma of the Head and Neck

Dreyfuss, Arnon I.; Clark, John R.; Wright, Joel E.; Norris, Charles M.; Busse, Paul M.; Lucarini, J.; Fallon, Barbara G.; Casey, D.; Andersen, Janet; Klein, Richard L.; Rosowsky, A.; Miller, Daniel; Frei, Emil

doi:10.7326/0003-4819-112-3-167

Cited by 115 publications

(16 citation statements)

References 20 publications

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“…The short half-life of the drug and its cell cycle phase-specific action favour prolonged infusion. This is supported by promising response rates of trials using high-dose 4-to 5-day or lowerdose multiweek infusions in the treatment of colorectal and head and neck tumours (Seifert et al, 1975;Al-Sarraf, 1988;Lokich et al, 1989;Dreyfuss et al, 1990). In addition, significantly less hematological and gastrointestinal side effects are seen with continuous infusion compared to bolus regimens (Lokich et al, 1989;Macdonald, 1989).…”

supporting

confidence: 52%

“…In colorectal cancer 5-day high-dose or prolonged (several weeks) continuous low-dose infusion have shown higher response rates and were better tolerated than standard 5-day monthly bolus regimen (Seifert et al, 1975;Lokich et al, 1989). In head and neck cancer the most potent drug combinations include continuous 5-FU (Kish et al, 1984;Dreyfuss et al, 1990) which was superior to bolus (Kish et al, 1985). Finally, a fraction of breast cancer patients refractory to 5-FU-containing combinations still responds to a prolonged low-dose infusion of 5-FU alone (Huan et al, 1989).…”

Section: Kinetic Analysismentioning

confidence: 99%

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Bioavailability and feasibility of subcutaneous 5-fluorouracil

Borner

Kneer²,

Crevoisier³

et al. 1993

Br J Cancer

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supporting

confidence: 52%

Section: Kinetic Analysismentioning

confidence: 99%

Bioavailability and feasibility of subcutaneous 5-fluorouracil

Borner

Kneer²,

Crevoisier³

et al. 1993

Br J Cancer

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“…Grades 3 and 4 stomatitis were lower compared to those commonly observed more than 80% seen in PF for head and neck cancers (Dreyfuss et al, 1990;Vokes et al, 1990;Chi et al, 1994). Furthermore, with a lower dosage of cisplatin and fewer courses of cisplatin-based chemotherapy, nephrotoxicity, ototoxicity and neurotoxicity were minimal.…”

Section: Discussionmentioning

confidence: 86%

Induction with mitomycin C, doxorubicin, cisplatin and maintenance with weekly 5-fluorouracil, leucovorin for treatment of metastatic nasopharyngeal carcinoma: a phase II study

Hong

Sheen

et al. 1999

Br J Cancer

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The combination of cisplatin and 5-fluorouracil (5-FU) (PF) is the most popular regimen for treating metastatic nasopharyngeal carcinoma (NPC) but it is limited by severe stomatitis and chronic cisplatin-related toxicity. A novel approach including induction with mitomycin C, doxorubicin and cisplatin (MAP) and subsequent maintenance with weekly 5-FU and leucovorin (FL) were designed with an aim to reduce acute and chronic toxicity of PF. Thirty-two patients of NPC with measurable metastatic lesions in the liver or lung were entered into this phase II trial. Mitomycin C 8 mg m −2 , doxorubicin 40 mg m −2 and cisplatin 60 mg m −2 were given on day 1 every 3 weeks as initial induction. After either four courses or remission was achieved, patients received weekly dose of 5-FU 450 mg m −2 and leucovorin 30 mg m −2 for maintenance until disease progression. With 105 courses of MAP given, 5% were accompanied by grade 3 and 0% were accompanied by grade 4 stomatitis. The dose-limiting toxicity of MAP was myelosuppression. Forty per cent of courses had grade 3 and 13% of courses had grade 4 leukopenia. No grade 3 or 4 cisplatin-related toxicity was observed. The overall response rate was 94% (95% confidence interval (CI) 84.9–100%) with a complete response rate (CR) of 6% (95% CI: 0–15.2%) and a good partial response (PR) rate of 28% (95% CI 11.7–44.6%), which was optionally defined as observance of only equivocal lesion identifiable under imaging study. Twenty-seven cases entered weekly FL maintenance phase. The median duration of maintenance with weekly FL was 38 weeks (8–91 weeks). There was no grade 3 or 4 toxicity noted during weekly FL. The median progression-free survival and overall survival were 11.6 ± 0.4 and 18.1 ± 3.6 months respectively. Six patients with a median follow-up of 19.8 months (9.6–41.0 months) were still alive and five of them had disease under control with FL. Good responders (CR and good PR) had better survival than less satisfactory responders (PR and stable disease) ( P = 0.05). From Cox’s multivariate regression analysis, the only significant prognostic factor for survival was good response to MAP ( P = 0.042). Liver metastasis was the only significant variable in the best subset regression model that predicted good response to MAP (CR and good PR) ( P = 0.027). MAP was an effective combination for metastatic NPC with minimal stomatitis and cisplatin-related toxicity but had significant myelosuppression. Weekly FL was a maintenance therapy with minimal side-effects. The response rate and overall survival of MAP-FL were better than series previously reported even when a subset of patients with poor prognosis was selected. MAP-FL's role as neoadjuvant or adjuvant therapy is worthy of further study. © 1999 Cancer Research Campaign

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“…The chemotherapeutic drug combination that we have decided to use in the present trial has been shown to be tolerable and active against various solid tumours, including pancreatic carcinoma as indicated in a recent phase II study in patients with metastatic disease (Hart et al, 1989;Dreyfuss et al, 1990;Vokes et al, 1992;Scheithauer et al, 1994;Andre et al, 1996). 5-FU is the most commonly used cytotoxic drug with an objective response rate of 10-20%.…”

Section: Discussionmentioning

confidence: 99%

Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil, leucovorin and cisplatin

et al. 2000

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The aim of the study was to evaluate the effectiveness and safety of a combined treatment modality including systemic chemotherapy with 5-fluorouracil (FU), leucovorin, cisplatin and external beam radiotherapy in patients with locally advanced pancreatic cancer. Systemic chemotherapy consisted of FU 400 mg m −2 and leucovorin 20 mgm −2 both given as intravenous bolus injection on days 1–4, plus cisplatin 20 mgm −2 administered as 90-min infusion on days 1–4. Treatment courses were repeated every 4 weeks × 6 unless prior evidence of progressive disease. Radiation therapy using megavolt irradiation of ≥ 6 MV photons with a 3- or 4-field technique was delivered during the second and third chemotherapy course, that was reduced in dose by 25%. Between October 1994 and July 1996, a total of 38 patients were entered onto this trial, all of whom were assessable for toxicity and survival. Eighteen of these (47%) had objective remissions to combined radiochemotherapy, including four CR (11%), 13 (34%) had stable disease and seven patients (18%) showed tumour progression during treatment. The median progression-free interval of the entire study population was 10 months (range 3–32), and median overall survival was 14.0 months (range 3–45+ months); 53% of all patients were alive at 12 months, and 18% of patients were alive at 24 months respectively. Severe haematological side-effects comprised neutropenia in 18%, thrombocytopenia in 8% and anaemia in 11%. The most frequent non-haematological side-effects were nausea/vomiting (WHO grade 3: 18%), and diarrhoea (grade 3: 13%). This combined radiochemotherapy regimen was tolerable and effective in patients with locally advanced pancreatic cancer. Since therapeutic results, in fact, compare favourably with other series, including surgical treatment of potentially resectable tumours, further evaluation of combined treatment modalities in the neoadjuvant setting seems warranted. © 2000 Cancer Research Campaign

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Continuous Infusion High-Dose Leucovorin with 5-Fluorouracil and Cisplatin for Untreated Stage IV Carcinoma of the Head and Neck

Cited by 115 publications

References 20 publications

Bioavailability and feasibility of subcutaneous 5-fluorouracil

Bioavailability and feasibility of subcutaneous 5-fluorouracil

Induction with mitomycin C, doxorubicin, cisplatin and maintenance with weekly 5-fluorouracil, leucovorin for treatment of metastatic nasopharyngeal carcinoma: a phase II study

Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil, leucovorin and cisplatin

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