Induction with mitomycin C, doxorubicin, cisplatin and maintenance with weekly 5 fluorouracil, leucovorin for treatment of metastatic nasopharyngeal carcinoma

A phase II study

R. L. Hong, T. S. Sheen, J. Y. Ko, M. M. Hsu, C. C. Wang, L. L. Ting

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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 acid 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-FLs role as neoadjuvant or adjuvant therapy is worthy of further study.

Original languageEnglish
Pages (from-to)1962-1967
Number of pages6
JournalBritish Journal of Cancer
Volume80
Issue number12
DOIs
Publication statusPublished - Aug 28 1999
Externally publishedYes

Fingerprint

Leucovorin
Mitomycin
Fluorouracil
Doxorubicin
Cisplatin
Maintenance
Stomatitis
Confidence Intervals
Therapeutics
Survival
Nasopharyngeal carcinoma
Liver
Leukopenia
Disease-Free Survival
Disease Progression
Multivariate Analysis
Survival Rate
Regression Analysis
Neoplasm Metastasis
Lung

Keywords

  • Chemotherapy
  • Cisplatin
  • Metastasis
  • Mitomycin
  • Nasopharyngeal carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Induction with mitomycin C, doxorubicin, cisplatin and maintenance with weekly 5 fluorouracil, leucovorin for treatment of metastatic nasopharyngeal carcinoma : A phase II study. / Hong, R. L.; Sheen, T. S.; Ko, J. Y.; Hsu, M. M.; Wang, C. C.; Ting, L. L.

In: British Journal of Cancer, Vol. 80, No. 12, 28.08.1999, p. 1962-1967.

Research output: Contribution to journalArticle

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abstract = "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 acid 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-FLs role as neoadjuvant or adjuvant therapy is worthy of further study.",
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AU - Hong, R. L.

AU - Sheen, T. S.

AU - Ko, J. Y.

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AU - Wang, C. C.

AU - Ting, L. L.

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N2 - 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 acid 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-FLs role as neoadjuvant or adjuvant therapy is worthy of further study.

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KW - Cisplatin

KW - Metastasis

KW - Mitomycin

KW - Nasopharyngeal carcinoma

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