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Biochemotherapy with Carmustine, Cisplatin, Dacarbazine, Tamoxifen and Low-dose Interleukin-2 for Patients with Metastatic Malignant Melanoma

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Author(s): Po-Jung Su | Jen-Shi Chen | Chuang-Chi Liaw | Hsien-Kun Chang | Hung-Ming Wang | Tsia-Sheng Yang | Yung-Chang Lin | Chi-Ting Liau | Hsin-Yi Yang | Kun-Yun Yeh | Ming-Mo Ho | Nai-Jun Chang | Cheng-Hsu Wang | John Wen-Chen Chang

Journal: Chang Gung Medical Journal
ISSN 2072-0939

Volume: 34;
Issue: 05;
Start page: 478;
Date: 2011;
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Keywords: malignant melanoma | carmustine | cisplatin | dacarbazine | tamoxifen | interleukin-2

ABSTRACT
Background: The toxicity and efficacy of biochemotherapy with low-dose interleukin-2for patients with metastatic malignant melanoma (MM) were studied.Method: Metastatic chemo-naïve MM patients were given biochemotherapy (BCDTregimen) with carmustine (BCNU), cisplatin (CDDP), dacarbazine (DTIC),and tamoxifen and interleukin-2 (IL-2) 18 Million International Units individed doses by subcutaneous injection three times a week for four weeks.BCDT consisted of BCNU (150 mg/m2, day l every 8 weeks), CDDP (25mg/m2, days l-3 every 4 weeks), DTIC (220 mg/m2, days 1-3 every 4 weeks)and tamoxifen 10 mg twice a day. Treatment was repeated for a total of 6cycles, or until disease progression or unbearable toxicity.Results: From Nov 2001 to July 2005, 40 pa t i ent s (20 men; 20 women) we r eenrolled. Their median age was 54 years (range 22-79 years). Subtypes ofmelanoma included 23 (57.5%) acral lentiginous, 11 (27.5%) nodular, 1(2.5%) mucosal, and 5 (12.5%) others. Grade 3-4 toxicities included neut r o p e n i a ( 2 7 . 5 % ) , a n e m i a ( 4 5 % ) , a n d t h r o m b o c y t o p e n i a ( 4 0 % ) .Constitutional IL-2 toxicities included indurate injection site (57.5%), fever(60%), chills (55%), itchy skin (42.5%), bone pain (32.5%) and myalgia(45%). Grade 1-2 hypotension was noted in 12.5% of patients. Eosinophilia(range 5% to 71%) was evident in 72.5% of patients. The response rate was32.5% inc luding 5% wi th a compl e t e r e spons e , 27.5% wi th a pa r t i a lresponse, and 17.5% with stable disease. The median progression-free survival was 6.2 months (95% CI: 2.9~9.6 months). The median overall survival was 11.3 months (95% CI: 7.0~15.6 months). Five patients (12.5%)who presented with oligo-metastasis achieved five-year survivals.Conclusions: Our data demonstrated that low-dose IL-2 plus BCDT is tolerable. A durableresponse and long-term survival can be achieved in a small subgroup ofpatients.
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