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A phase I study of bevacizumab, everolimus and panitumumab in advanced solid tumors.

Publication ,  Journal Article
Vlahovic, G; Meadows, KL; Uronis, HE; Morse, MA; Blobe, GC; Riedel, RF; Zafar, SY; Alvarez-Secord, A; Gockerman, J; Starodub, AN; Ready, NE ...
Published in: Cancer Chemother Pharmacol
July 2012

PURPOSE: Preclinical data suggest concurrent inhibition of VEGF, mTOR and EGFR pathways may augment antitumor and antiangiogenic effects compared to inhibition of each pathway alone. This study evaluated the maximum tolerated dose/recommended phase II dose and safety and tolerability of bevacizumab, everolimus and panitumumab drug combination. METHODS: Subjects with advanced solid tumors received escalating doses of everolimus and flat dosing of panitumumab at 4.8 mg/kg and bevacizumab at 10 mg/kg every 2 weeks. Dose-limiting toxicities (DLTs) were assessed in cycle 1; toxicity evaluation was closely monitored throughout treatment. Treatment continued until disease progression or undesirable toxicity. RESULTS: Thirty-two subjects were evaluable for toxicity; 31 subjects were evaluable for tumor response. DLTs were observed in cohorts with everolimus at 10 and 5 mg daily and included grade 3 mucositis, skin rash and thrombocytopenia. Therefore, everolimus was dose-reduced to 5 mg three times weekly, which improved the tolerability of the treatment regimen. Common adverse events were skin rash/pruritus (91 %), mucositis/stomatitis (75 %), hypomagnesemia (72 %), hypocalcemia (56 %) and hypokalemia (50 %). There were 3 partial responses; an additional 10 subjects had stable disease ≥6 months. Three subjects with ovarian cancer and one with endometrial cancer achieved prolonged disease control ranging from 11 to >40 months. CONCLUSIONS: The recommended phase II dose is everolimus at 5 mg three times weekly plus panitumumab at 4.8 mg/kg and bevacizumab at 10 mg/kg every 2 weeks. This dosing regimen has an acceptable safety and tolerability profile and appears to have moderate the clinical activity in refractory tumors.

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Published In

Cancer Chemother Pharmacol

DOI

EISSN

1432-0843

Publication Date

July 2012

Volume

70

Issue

1

Start / End Page

95 / 102

Location

Germany

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Sirolimus
  • Panitumumab
  • Oncology & Carcinogenesis
  • Neoplasms
  • Mucositis
  • Middle Aged
  • Male
  • Hypokalemia
 

Citation

APA
Chicago
ICMJE
MLA
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Vlahovic, G., Meadows, K. L., Uronis, H. E., Morse, M. A., Blobe, G. C., Riedel, R. F., … Hurwitz, H. I. (2012). A phase I study of bevacizumab, everolimus and panitumumab in advanced solid tumors. Cancer Chemother Pharmacol, 70(1), 95–102. https://doi.org/10.1007/s00280-012-1889-8
Vlahovic, Gordana, Kellen L. Meadows, Hope E. Uronis, Michael A. Morse, Gerard C. Blobe, Richard F. Riedel, S Yousuf Zafar, et al. “A phase I study of bevacizumab, everolimus and panitumumab in advanced solid tumors.Cancer Chemother Pharmacol 70, no. 1 (July 2012): 95–102. https://doi.org/10.1007/s00280-012-1889-8.
Vlahovic G, Meadows KL, Uronis HE, Morse MA, Blobe GC, Riedel RF, et al. A phase I study of bevacizumab, everolimus and panitumumab in advanced solid tumors. Cancer Chemother Pharmacol. 2012 Jul;70(1):95–102.
Vlahovic, Gordana, et al. “A phase I study of bevacizumab, everolimus and panitumumab in advanced solid tumors.Cancer Chemother Pharmacol, vol. 70, no. 1, July 2012, pp. 95–102. Pubmed, doi:10.1007/s00280-012-1889-8.
Vlahovic G, Meadows KL, Uronis HE, Morse MA, Blobe GC, Riedel RF, Zafar SY, Alvarez-Secord A, Gockerman J, Starodub AN, Ready NE, Anderson EL, Bendell JC, Hurwitz HI. A phase I study of bevacizumab, everolimus and panitumumab in advanced solid tumors. Cancer Chemother Pharmacol. 2012 Jul;70(1):95–102.
Journal cover image

Published In

Cancer Chemother Pharmacol

DOI

EISSN

1432-0843

Publication Date

July 2012

Volume

70

Issue

1

Start / End Page

95 / 102

Location

Germany

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Sirolimus
  • Panitumumab
  • Oncology & Carcinogenesis
  • Neoplasms
  • Mucositis
  • Middle Aged
  • Male
  • Hypokalemia