Phase II study of sorafenib in patients with metastatic or recurrent sarcomas

Robert G. Maki, David R. D'Adamo, Mary L. Keohan, Michael Saulle, Scott M. Schuetze, Samir D. Undevia, Michael B. Livingston, Matthew M. Cooney, Martee L. Hensley, Monica M. Mita, Chris H. Takimoto, Andrew Kraft, Anthony D. Elias, Bruce Brockstein, Nathalie E. Blachère, Mark A. Edgar, Lawrence H. Schwartz, Li Xuan Qin, Cristina R. Antonescu, Gary K. Schwartz

Research output: Contribution to journalArticle

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Abstract

Purpose: Since activity of sorafenib was observed in sarcoma patients in a phase I study, we performed a multicenter phase II study of daily oral sorafenib in patients with recurrent or metastatic sarcoma. Patients and Methods: We employed a multiarm study design, each representing a sarcoma subtype with its own Simon optimal two-stage design. In each arm, 12 patients who received 0 to 1 prior lines of therapy were treated (0 to 3 for angiosarcoma and malignant peripheral-nerve sheath tumor). If at least one Response Evaluation Criteria in Solid Tumors (RECIST) was observed, 25 further patients with that sarcoma subtype were accrued. Results: Between October 2005 and November 2007, 145 patients were treated; 144 were eligible for toxicity and 122 for response. Median age was 55 years; female-male ratio was 1.8:1. The median number of cycles was 3. Five of 37 patients with angiosarcoma had a partial response (response rate, 14%). This was the only arm to meet the RECIST response rate primary end point. Median progression-free survival was 3.2 months; median overall survival was 14.3 months. Adverse events (typically dermatological) necessitated dose reduction for 61% of patients. Statistical modeling in this limited patient cohort indicated sorafenib toxicity was correlated inversely to patient height. There was no correlation between phosphorylated extracellular signal regulated kinase expression and response in six patients with angiosarcoma with paired pre- and posttherapy biopsies. Conclusion: As a single agent, sorafenib has activity against angiosarcoma and minimal activity against other sarcomas. Further evaluation of sorafenib in these and possibly other sarcoma subtypes appears warranted, presumably in combination with cytotoxic or kinase-specific agents.

Original languageEnglish (US)
Pages (from-to)3133-3140
Number of pages8
JournalJournal of Clinical Oncology
Volume27
Issue number19
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

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Sarcoma
Hemangiosarcoma
sorafenib
Extracellular Signal-Regulated MAP Kinases
Neurilemmoma
Disease-Free Survival
Phosphotransferases
Biopsy
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Maki, R. G., D'Adamo, D. R., Keohan, M. L., Saulle, M., Schuetze, S. M., Undevia, S. D., ... Schwartz, G. K. (2009). Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. Journal of Clinical Oncology, 27(19), 3133-3140. https://doi.org/10.1200/JCO.2008.20.4495

Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. / Maki, Robert G.; D'Adamo, David R.; Keohan, Mary L.; Saulle, Michael; Schuetze, Scott M.; Undevia, Samir D.; Livingston, Michael B.; Cooney, Matthew M.; Hensley, Martee L.; Mita, Monica M.; Takimoto, Chris H.; Kraft, Andrew; Elias, Anthony D.; Brockstein, Bruce; Blachère, Nathalie E.; Edgar, Mark A.; Schwartz, Lawrence H.; Qin, Li Xuan; Antonescu, Cristina R.; Schwartz, Gary K.

In: Journal of Clinical Oncology, Vol. 27, No. 19, 01.07.2009, p. 3133-3140.

Research output: Contribution to journalArticle

Maki, RG, D'Adamo, DR, Keohan, ML, Saulle, M, Schuetze, SM, Undevia, SD, Livingston, MB, Cooney, MM, Hensley, ML, Mita, MM, Takimoto, CH, Kraft, A, Elias, AD, Brockstein, B, Blachère, NE, Edgar, MA, Schwartz, LH, Qin, LX, Antonescu, CR & Schwartz, GK 2009, 'Phase II study of sorafenib in patients with metastatic or recurrent sarcomas', Journal of Clinical Oncology, vol. 27, no. 19, pp. 3133-3140. https://doi.org/10.1200/JCO.2008.20.4495
Maki RG, D'Adamo DR, Keohan ML, Saulle M, Schuetze SM, Undevia SD et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. Journal of Clinical Oncology. 2009 Jul 1;27(19):3133-3140. https://doi.org/10.1200/JCO.2008.20.4495
Maki, Robert G. ; D'Adamo, David R. ; Keohan, Mary L. ; Saulle, Michael ; Schuetze, Scott M. ; Undevia, Samir D. ; Livingston, Michael B. ; Cooney, Matthew M. ; Hensley, Martee L. ; Mita, Monica M. ; Takimoto, Chris H. ; Kraft, Andrew ; Elias, Anthony D. ; Brockstein, Bruce ; Blachère, Nathalie E. ; Edgar, Mark A. ; Schwartz, Lawrence H. ; Qin, Li Xuan ; Antonescu, Cristina R. ; Schwartz, Gary K. / Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 19. pp. 3133-3140.
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AU - Schuetze, Scott M.

AU - Undevia, Samir D.

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AU - Edgar, Mark A.

AU - Schwartz, Lawrence H.

AU - Qin, Li Xuan

AU - Antonescu, Cristina R.

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