Chemotherapy with cyclophosphamide, vincristine and dacarbazine for malignant paraganglioma and pheochromocytoma: systematic review and meta-analysis

Clin Endocrinol (Oxf). 2014 Nov;81(5):642-51. doi: 10.1111/cen.12542. Epub 2014 Jul 30.

Abstract

Background: Chemotherapy with cyclophosphamide, vincristine and dacarbazine (CVD) can be used for palliative treatment of malignant pheochromocytoma and paraganglioma. However, the precise effect of this chemotherapeutic regimen on tumour volume is unclear. The main objective of this study was to perform a systematic review and meta-analysis assessing the effect of chemotherapy with CVD on tumour volume in patients with malignant paraganglioma/pheochromocytoma.

Methods: A literature search was performed in October 2013 to identify potentially relevant studies. Main outcomes were the pooled percentages of complete response, partial response and stable disease after chemotherapy with CVD. A meta-analysis was performed with an exact likelihood approach using a logistic regression. Pooled percentages with 95% confidence intervals (CI) were reported.

Results: Four studies concerning a total of 50 patients with malignant paraganglioma/pheochromocytoma reported on treatment with a combination of CVD chemotherapy. A meta-analysis of the effect of chemotherapy on tumour volume showed pooled percentages of complete response, partial response and stable disease of, respectively, 4% (95% CI: 1%-15%), 37%(95% CI: 25%-51%) and 14% (95% CI: 7%-27%). Only two studies concerning a total of 35 patients assessed the response on catecholamine excess; pooled percentages for complete, partial and stable hormonal response were 14% (95% CI: 6%-30%), 40% (95% CI: 25%-57%) and 20% (95% CI: 10%-36%), respectively. Duration of response was also reported in only two studies with a median duration of response of 20 months and 40 months.

Conclusions: Data on the effects of a combination of CVD chemotherapy on malignant paraganglioma/pheochromocytoma suggest that a partial response concerning tumour volume can be achieved in about 37% of patients and a partial response on catecholamine excess in about 40% of patients. However, in the included studies, the protocol when to initiate treatment was not well described. Therefore, it cannot be excluded that the reported effect of chemotherapy on tumour volume reflects the natural course of the disease, at least partially.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adrenal Gland Neoplasms / drug therapy*
  • Adrenal Gland Neoplasms / epidemiology
  • Adrenal Gland Neoplasms / pathology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Catecholamines / metabolism
  • Cyclophosphamide / therapeutic use
  • Dacarbazine / therapeutic use
  • Humans
  • Paraganglioma / drug therapy*
  • Paraganglioma / epidemiology
  • Paraganglioma / pathology
  • Pheochromocytoma / drug therapy*
  • Pheochromocytoma / epidemiology
  • Pheochromocytoma / pathology
  • Tumor Burden
  • Vincristine / therapeutic use

Substances

  • Catecholamines
  • Vincristine
  • Dacarbazine
  • Cyclophosphamide

Supplementary concepts

  • CVD protocol