In vitro drug sensitivity predicts response and survival after individualized sensitivity-directed chemotherapy in metastatic melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group

Clin Cancer Res. 2006 Sep 15;12(18):5454-63. doi: 10.1158/1078-0432.CCR-05-2763.

Abstract

Purpose: In vitro sensitivity assays are promising tools to predict the individual outcome of different chemotherapy regimens. However, a direct association between in vitro and in vivo chemosensitivity has to be shown by clinical studies. This multicenter phase II trial was aimed to investigate the efficacy of a sensitivity-directed, first-line chemotherapy in metastasized melanoma patients, and to prove an association between in vitro sensitivity and therapy outcome.

Patients and methods: The primary study end point was objective response; secondary end points were safety, overall survival, and progression-free survival. Viable tumor cells obtained from metastatic lesions were tested for chemosensitivity to seven single drugs and five drug combinations using an ATP-based luminescence viability assay.

Results: Out of 82 recruited patients (intention-to-treat), 57 received assay-directed chemotherapy and 53 were evaluable for all study end points (per protocol). The drug combinations used were gemcitabine+treosulfan, paclitaxel+cisplatin, paclitaxel+doxorubicin, and gemcitabine+cisplatin. The per protocol population could be divided into 22 (42%) chemosensitive and 31 (58%) chemoresistant patients by an arbitrary chemosensitivity index. Objective response was 36.4% in chemosensitive patients compared with 16.1% in chemoresistant patients (P=0.114); progression arrest (complete response+partial response+stable disease) was 59.1% versus 22.6% (P=0.01). Chemosensitive patients showed an increased overall survival of 14.6 months compared with 7.4 months in chemoresistant patients (P=0.041).

Conclusion: In vitro chemosensitivity testing may be worthy of further exploration to see if it could be a useful tool to predict the outcome of melanoma patients treated with a sensitivity-directed chemotherapy. Therefore, these preliminary results will be evaluated by a planned phase III trial using a randomized, standard-regimen controlled setting.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Busulfan / analogs & derivatives
  • Busulfan / therapeutic use
  • Cisplatin / therapeutic use
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / physiology
  • Drug Screening Assays, Antitumor* / methods
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Melanoma / drug therapy*
  • Melanoma / mortality
  • Middle Aged
  • Paclitaxel / therapeutic use
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Survival Analysis
  • Treatment Outcome

Substances

  • Deoxycytidine
  • Doxorubicin
  • treosulfan
  • Busulfan
  • Paclitaxel
  • Cisplatin
  • Gemcitabine