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

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 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

Validation of a new prognostic index score for disseminated nasopharyngeal carcinoma

“…However, as Cohort 2 was used for validation of the score and all the patients in Cohort 2 were treated, we elected to reanalyse Cohort 1 to restrict the derivation of a new prognostic index score to only patients given chemotherapy. The reason for the reanalysis is that chemotherapy has an impact on survival outcome in patients with disseminated NPC, although there are no randomised comparison studies between chemotherapy and best supportive care (Fandi et al, 1994;Hong et al, 1999). This is also supported by the fact that incorporation of chemotherapy in locally advanced disease has been shown to improve progression-free and overall survival Cohort 1 Figure 1 Survival curves for Cohorts 1 and 2.…”

Prognostic Value of Multidrug Resistance 1, Glutathione-<i>S</i>-Transferase-π and p53 in Advanced Nasopharyngeal Carcinoma Treated with Systemic Chemotherapy

“…Among them, 34 patients had received cisplatin-containing regimens including PF (7 cases) and MAP-FL (28 cases). MAP-FL, which also contained doxorubicin, was the regimen of a phase II clinical trial conducted at our institute [7]. Details of the chemotherapy regimen are listed in table 2.…”

“…The 2-year survival rate of patients with advanced NPC is around 10% [2, 3, 5, 6, 7, 8]. Many of these patients, although initially responsive to chemotherapy, do not enjoy a durable remission.…”

“…Although NPC is chemosensitive, the outcome of patients with recurrent or metastatic disease is not satisfactory [5, 6, 7, 8]. The 2-year survival rate of patients with advanced NPC is around 10% [2, 3, 5, 6, 7, 8].…”

Emerging treatment options for nasopharyngeal carcinoma

“…Fluoropyrimidines are thought to also function as angiogenesis inhibitors 96. Results from studies in Taiwan97 and Singapore98 have shown great promise in terms of median survival rates in metastatic NPC. The use of biomarkers has provided new possibilities for tailoring treatments for patients who are most likely to benefit.…”