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Phase I study of the combination of docetaxel, temozolomide and cisplatin in patients with metastatic melanoma

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Abstract

Purpose

In a search for more effective combination chemotherapy for the treatment of metastatic melanoma, we conducted a phase I trial of a novel combination of docetaxel, temozolomide, and cisplatin.

Methods

Patients with inoperable or recurrent metastatic melanoma with a Zubrod performance status of 2 or less and adequate organ function were eligible. The dose of docetaxel was escalated between cohorts of patients, and the doses of temozolomide and cisplatin were fixed. A standard 3 + 3 dose escalation design was used to determine the maximum tolerated dose (MTD).

Results

Among 23 patients who were enrolled, 21 were evaluable for toxicity. Eighteen patients (78%) had stage IV-M1c disease. The dose-limiting toxicities were myelosuppression and pulmonary embolism. The MTD was 30 mg/m2 docetaxel on days 1, 8, and 15 when given with 150 mg/m2 temozolomide on days 1–5, and 20 mg/m2 cisplatin on days 1–4, repeating every 4 weeks. Among 19 patients evaluated for response, 6 (32%) had partial responses and 5 (26%) had stable disease. Among 14 chemo-naive patients, 6 (43%) had a partial response and 4 (29%) had stable disease. Nine patients developed brain metastases by the time of the last follow-up evaluation, and the median time to brain metastases for all 19 evaluable patients has not been reached.

Conclusions

This combination was well tolerated and appears to be a promising treatment for patient with metastatic melanoma.

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Acknowledgments

The authors thank Ms. Virginia M. Mohlere for her editorial assistance.

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Authors and Affiliations

  1. Department of Melanoma Medical Oncology, Unit 430, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA

    Kevin B. Kim, Wen-Jen Hwu, Nicholas E. Papadopoulos, Agop Y. Bedikian, Luis H. Camacho, Ingrid M. Hernandez, Angela M. Frost, Monica A. Jack & Patrick Hwu

  2. Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Chaan Ng

Authors
  1. Kevin B. Kim
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  2. Wen-Jen Hwu
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  3. Nicholas E. Papadopoulos
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  4. Agop Y. Bedikian
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  5. Luis H. Camacho
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  6. Chaan Ng
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  7. Ingrid M. Hernandez
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  8. Angela M. Frost
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  9. Monica A. Jack
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  10. Patrick Hwu
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Corresponding author

Correspondence to Kevin B. Kim.

Additional information

This study was supported by Sanofi-Aventis.

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Kim, K.B., Hwu, WJ., Papadopoulos, N.E. et al. Phase I study of the combination of docetaxel, temozolomide and cisplatin in patients with metastatic melanoma. Cancer Chemother Pharmacol 64, 161–167 (2009). https://doi.org/10.1007/s00280-008-0861-0

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  • DOI: https://doi.org/10.1007/s00280-008-0861-0

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