Low-dose chemotherapy with methotrexate and vinblastine for patients with refractory desmoid tumors: A second report of relationship between efficacy and various factors

Summary

The aim of this study was to reveal the clinical outcome of low-dose chemotherapy with methotrexate (MTX) + vinblastine (VBL), and determine the useful factors to predict the efficacy including CTNNB1 mutation status. Since 2003, 167 cases were histologically diagnosed as DF. Among them, 36 cases were treated with MTX (30mg/M2) +VBL (6mg/M2) chemotherapy. Treatment interval was basically 2 weeks according to our previous study. Effectiveness was evaluated with MRI and/or CT every 3 months according to Response Evaluation Criteria in Solid Tumors (RECIST). Frozen or FFPE (Formalin-Fixed Paraffin-Embedded) specimens obtained at biopsy or previous surgery were subjected to the analyses for CTNNB1 mutation status by Sanger method. Clinical outcome and factors correlating with the efficacy were analyzed. Among 36 cases with this chemotherapy, male was 13, mean age at the treatment was 36±18 years. Mean maximum diameter of tumor was 15±18 cm. Twenty-nine cases (81%) harbored CTNNB1 or APC mutation. Mean treatment duration and cycles of MTX+VBL were 20 months and 29 cycles, respectively. According to RECIST, PD in 2, PR 1n 15, and SD in 19. According to CTCAE, Grade 3 or more adverse events were observed in only one case. CTNNB1 mutation status, gender, age, size, and location did not affect the outcome of RECIST. Longer treatment duration and cycles of chemotherapy were significantly associated with the outcome (P = 0.002 and 0.004, respectively). In 15 cases of PR, recurrent tumors significantly took longer time to get efficacy (P = 0.027), and tumors arising in trunk and extremities tended to take longer time (P = 0.1). Low-dose MTX+VBL chemotherapy is effective and feasible treatment for refractory DF regardless of CTNNB1 mutation status. Occasionally it takes time to obtain objective response.