Phase II trial of gemcitabine and docetaxel with bevacizumab in soft tissue sarcoma Journal Article

Authors: Dickson, M. A.; D'adamo, D. R.; Keohan, M. L.; D'Angelo, S. P.; Carvajal, R. D.; Gounder, M. M.; Maki, R. G.; Qin, L. X.; Lefkowitz, R. A.; Mckennan, O. R.; Hirst, C. M.; Schwartz, G. K.; Tap, W. D.
Article Title: Phase II trial of gemcitabine and docetaxel with bevacizumab in soft tissue sarcoma
Abstract: Gemcitabine (G) and docetaxel (D) are commonly used to treat recurrent/metastatic soft tissue sarcoma. This study tested the hypothesis that outcomes would be improved by addition of bevacizumab (B). The initial design was randomized double-blind trial of G + D + B versus G + D + placebo. Due to slow accrual this was modified to single-arm open-label G + D + B. Eligible patients had diagnosis of leiomyosarcoma, pleomorphic undifferentiated sarcoma, pleomorphic liposarcoma, or angiosarcoma. Treatment was B 15 mg/kg on d1, G 900 mg/m2 on d1 and d8, and D 75 mg/m2 on d8, q21d. Primary endpoint was progression-free survival (PFS) at 6 months and would be met if ≥17 patients were progression-free at 6 m. Secondary endpoints are response rate, PFS at 3 m, overall survival, and toxicity. Of 44 patients enrolled, 35 were treated with GDB and evaluable for safety and efficacy. Median age was 55, 50% male, most ECOG 0. Toxicity is mostly myelosuppression with one deep vein thrombosis and one small bowel perforation possibly related to B. There were 17 partial responses (49%) by RECIST 1.1. Among 35 patients, the number who remained on study and progression-free was 24 at 3 m and 15 at 6 m. 9 withdrew prior to 6 m for reasons other than toxicity or progression. PFS at 6 m was 65% (95% CI: 51-85%). The primary endpoint of 6 m PFS was not met due to censoring of patients who withdrew. However PFS at 3 m (76%) was promising and response rate was higher than expected from G + D. © 2015 Mark A. Dickson et al.
Keywords: adult; clinical article; controlled study; aged; overall survival; fatigue; sorafenib; bevacizumab; doxorubicin; placebo; drug efficacy; drug safety; gemcitabine; dacarbazine; edema; progression free survival; phase 2 clinical trial; anemia; bone marrow suppression; bleeding; mucosa inflammation; randomized controlled trial; thrombocytopenia; deep vein thrombosis; angiosarcoma; ifosfamide; docetaxel; alanine aminotransferase blood level; hyperglycemia; lymphocytopenia; pneumonia; sarcoma; alanine aminotransferase; aspartate aminotransferase; hypoalbuminemia; add on therapy; thrombosis; drug infusion; soft tissue sarcoma; alkaline phosphatase blood level; leiomyosarcoma; double blind procedure; digestive system perforation; liposarcoma; cellulitis; neck pain; pegfilgrastim; diverticulitis; human; male; female; priority journal; article
Journal Title: Sarcoma
Volume: 2015
ISSN: 1357-714X
Publisher: Hindawi Publishing Corporation  
Date Published: 2015-01-01
Start Page: 532478
Language: English
DOI: 10.1155/2015/532478
PROVIDER: scopus
PMCID: PMC4446476
PUBMED: 26074722
Notes: Export Date: 2 July 2015 -- Source: Scopus
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MSK Authors
  1. Li-Xuan Qin
    116 Qin
  2. Mary Louise Keohan
    66 Keohan
  3. Mrinal M Gounder
    74 Gounder
  4. Mark Andrew Dickson
    79 Dickson
  5. William Douglas Tap
    129 Tap
  6. Catherine Mackensie Hirst
    3 Hirst