Oral metronomic cyclophosphamide in elderly with metastatic melanoma

Invest New Drugs. 2010 Oct;28(5):684-9. doi: 10.1007/s10637-009-9298-5. Epub 2009 Aug 12.

Abstract

Introduction: In Western countries, the number of frail elderly people with metastatic melanoma (MM) keeps increasing. Conventional chemotherapy frequently induces imbalance in frail physiological cases. We propose to treat these patients with oral metronomic cyclophosphamide.

Patients and methods: This retrospective study analyses the data of patients with unresectable MM who received 50 to 100 mg of cyclophosphamide a day, 3 weeks out of 4. Main evaluation criterion was safety. Secondary evaluation criteria were objective response rate and overall survival.

Results: Thirteen patients were included (median age: 80, 5 AJCC stage III and 8 AJCC stage IV). Clinical and biological safety were good, leading to long home staying and rare treatment discontinuations. Main toxicity observed was lymphopenia; no opportunist infection occurred. The control rate was 46%: one partial response and five stable diseases (median: 10 months). Survival after beginning of treatment ranged from 4 to 37 months (median: 8 months).

Discussion: Literature about MM in frail elderly is limited. Still, specific treatment is necessary. Cyclophosphamide in metronomic schema was well tolerated. The response rate was difficult to assess (small population) but several patients presented with long lasting stabilisation. The mechanisms of action of this treatment are original, associating antiangiogenic action and immunomodulation.

Conclusion: Cyclophosphamide in metronomic schema showed good safety results for this frail population. Oral treatment enabled patients to stay at home longer and limited hospitalisation time. A larger controlled study will be necessary to confirm these encouraging results in elderly with MM, a classical chemoresistant tumor.

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Antineoplastic Agents, Alkylating / adverse effects
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / pharmacology
  • Cyclophosphamide / therapeutic use*
  • Female
  • Humans
  • Immunomodulation / drug effects
  • Male
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Melanoma / pathology*
  • Neoplasm Metastasis
  • Survival Analysis

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Alkylating
  • Cyclophosphamide