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Phase I trial of biochemotherapy with cisplatin, temozolomide, and dose escalation of nab-paclitaxel combined with interleukin-2 and interferon-α in patients with metastatic melanoma

Alrwas, Anasa; Papadopoulos, Nicholas E.b; Cain, Suzanneb; Patel, Sapna P.b; Kim, Kevin B.b; Deburr, Tawania L.c; Bassett, Roland Jrd; Hwu, Wen-Jenb; Bedikian, Agop Y.b; Davies, Michael A.b; Woodman, Scott E.b; Hwu, Patrickb

doi: 10.1097/CMR.0000000000000062
ORIGINAL ARTICLES: Clinical research

The primary objective of this study was to determine the safety, toxicity, and maximum tolerated dose of nanoparticle albumin-bound (nab)-paclitaxel as part of biochemotherapy for metastatic melanoma and to determine whether substituting nab-paclitaxel for less potent agents could increase response rates and duration. Treatment consisted of intravenous cisplatin (20 mg/m2) on days 1–4, oral temozolomide (250 mg/m2) on days 1–3, subcutaneous interferon-α (5×106 IU/m2) on days 1–5, and continuous intravenous interleukin-2 (9×106 IU/m2) for 96 h on days 1–4. A standard 3+3 dose escalation method was used; the nab-paclitaxel starting dose was 100 mg/m2 on day 1 and 70 mg/m2 on day 5. The treatment cycle was repeated every 3 weeks and toxicity was assessed weekly. Ten patients were enrolled. Dose-limiting toxicities included diarrhea, transaminasemia, and neutropenia. The maximum tolerated dose was not identified because the nab-paclitaxel dose on day 1 at the lowest planned dose (80 mg/m2) caused dose-limiting toxicity in two of five patients. Of the nine patients who were evaluable for response, five had a partial response. The median time to disease progression was 5.30 months and the median overall survival was 8.73 months. Six patients developed central nervous system metastasis at a median of 5.33 months after treatment initiation. Biochemotherapy including nab-paclitaxel according to the doses and schedule regimen used in the present study has significant toxicity. Substituting dacarbazine with temozolomide did not prevent central nervous system metastasis in patients with metastatic melanoma.

aHealth Science Center, University of Oklahoma, Oklahoma City, Oklahoma

Departments of bMelanoma Medical Oncology

cPalliative Care and Rehabilitative Medicine

dBiostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

This study was accepted to the American Society of Clinical Oncology Annual Meeting (ASCO), 1–5 June 2012, Chicago, IL (ASCO 2012, Abstract ID: e19009).

Correspondence to Nicholas E. Papadopoulos, MD, Department of Melanoma Medical Oncology, Unit 430, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA Tel: +1 713 792 2921; fax: +1 713 745 1046; e-mail:

Received August 29, 2013

Accepted February 7, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins