Low Dose Methotrexate and Vinblastine, Given Weekly to PatientsWith Desmoid Tumours, is Associated With Major Toxicity

Abstract

Purpose: To evaluate the tolerance of a low dose chemotherapy regimen for desmoid tumours. Patients and methods: Patients with desmoids for whom radical resection was impossible or related to extensive mutilation were treated with chemotherapy. Treatment consisted of intravenous methotrexate at a dose of 50 mg and vinblastine at a dose of 10 mg weekly, scheduled to be given for a total period of 1 year. Doses were reduced and/or delayed on an individual basis, depending on the observed type of toxicity. Results: Ten patients (six males; four females), median age 43 years (range17-75), median WHO performance score 1 (range 0-1), were treated. None of them was able to complete the treatment as scheduled, due to observed side effects, while in two patients treatment was also discontinued because of progressive disease. In six patients, less than 50% of the projected administrations and dose could be given. Severe organ toxicity was noted in three patients (one interstitial pneumonitis, two toxic hepatitis), which, however, was reversible in all cases. Discussion: Methotrexate and vinblastine given at this dose and schedule lead to an unacceptable level of toxicity for a long-term treatment, and cannot be recommended for standard use.

Clinical benefit of methotrexate plus vinorelbine chemotherapy for desmoid fibromatosis (DF) and correlation of treatment response with MRI

“…Treatment with low-dose MTX/VNL is well tolerated with minimal toxicity. Prior reports of MTX-based treatment suggest excessive toxicity 14,19 -however, this may have been due to inclusion of heavily pretreated patients, higher doses, and shorter intervals between cycles. In our study, there were no grade 3/4 toxicities observed.…”

“…In comparison, the use of vinblastine does not appear to be as well tolerated compared to VNL, with higher toxicity rates, especially neurotoxicity, hepatotoxicity, and neutropenia; however, this may also reflect higher doses and frequent scheduling. 1,10,12,14,19 Evaluating response to treatment of DF radiologically is in evolution. In this study, independent radiology review demonstrated that treatment response of DF to MTX/VNL correlated highly with V tumor and T2 intensity evaluated by MRI, findings also supported by Sheth.…”

Biology and Treatment of Aggressive Fibromatosis or Desmoid Tumor

“…166 Methotrexate combined with vinblastine or vinorelbine is more difficult to deliver over a prolonged course in adults because of toxicity. 143,167 Other agents include more aggressive chemotherapy such as anthracyclines, gemcitabine, and even ifosfamide in rare cases. 18,129,130,141,[145][146][147]168,169 Tyrosine kinase inhibitors also have activity in some DTF cases, and meaningful responses have been described.…”

Desmoid Tumors: Clinical Features and Treatment Options for Advanced Disease

“…The largest series showed at least stable disease in 18 of 27 patients, with eight of 27 patients being free from progression at a median of 43 months [39]. However, it has been questioned whether this regimen can also be applied safely in adults because the combination of vinblastine and methotrexate is quite toxic over time and patients generally cannot complete the recommended year of therapy [40]. Alternatively, the combination of vinorelbine and methotrexate can be administered and is likely much less toxic.…”