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
- 15 September 2006
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 12 (18), 5454-5463
- https://doi.org/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.Keywords
Other Versions
This publication has 28 references indexed in Scilit:
- Chemotherapy Sensitivity and Response Assays: Are the ASCO Guidelines for Clinical Trial Design Too Restrictive?Journal of Clinical Oncology, 2005
- In Vitro Drug Resistance Versus Chemosensitivity: Two Sides of Different CoinsJournal of Clinical Oncology, 2005
- Chemosensitivity and Resistance Assays: A Systematic Review?Journal of Clinical Oncology, 2005
- Resisting a Fundamentalist PolicyJournal of Clinical Oncology, 2005
- Penetration of dacarbazine and its active metabolite 5-aminoimidazole-4-carboxamide into cutaneous metastases of human malignant melanomaCancer, 2001
- New Guidelines to Evaluate the Response to Treatment in Solid TumorsJNCI Journal of the National Cancer Institute, 2000
- Treosulfan is an effective alkylating cytostatic for malignant melanoma in vitro and in vivoMelanoma Research, 1999
- Use of an ex vivo ATP luminescence assay to direct chemotherapy for recurrent ovarian cancerAnti-Cancer Drugs, 1998
- Correlation of the clinical response to chemotherapy in breast cancer with ex vivo chemosensitivityAnti-Cancer Drugs, 1996
- Complete remission seven years after treatment for metastatic malignant melanomaCancer, 1996