Phase II trial of Sorafenib in conjunction with chemotherapy and as maintenance therapy in extensive-stage small cell lung cancer

Neelesh Sharma, Nathan Pennell, Myles Nickolich, Balazs Halmos, Patrick Ma, Tarek Mekhail, Pingfu Fu, Afshin Dowlati

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objectives Sorafenib is a multi-tyrosine kinase inhibitor of Raf kinase, VEGFR, and PDGFR. Angiogenesis is important for growth and progression of SCLC. This trial was conducted to evaluate whether the combination of cisplatin and etoposide plus concurrent and sequential sorafenib could prolong survival in patients with previously untreated SCLC. Methods Previously untreated patients with extensive stage SCLC were treated with cisplatin and etoposide days 1, 2, 3 for four cycles, concurrent with sorafenib 200 mg orally bid starting day 1 cycle 1. Patients with no disease progression after four cycles continued sorafenib 400 mg orally bid as maintenance for maximum of 12 months. The primary endpoint was 1 year survival with response rate and safety as secondary endpoints. Results A total of 18 patients were enrolled with 17 evaluable patients. One patient had a complete response, seven patients had a partial response (overall response rate of 47 %) and one patient had stable disease. Overall median survival was 7.4 months and 1 year survival was 25 %. The most common treatment-related adverse events included fatigue, anorexia, rash, diarrhea, neutropenia and weight loss. Grade 5 GI bleeding, pulmonary hemorrhage and neutropenia occurred in one pt (6 %) each. Accrual was halted on the basis of safety profile as well as preliminary efficacy data. Conclusions The combination of platinum based chemotherapy and sorafenib has significant toxicity at current dose levels and is associated with disappointing efficacy data.

Original languageEnglish (US)
Pages (from-to)362-368
Number of pages7
JournalInvestigational New Drugs
Volume32
Issue number2
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Small Cell Lung Carcinoma
Drug Therapy
Survival
Etoposide
Therapeutics
Neutropenia
Cisplatin
raf Kinases
Hemorrhage
Safety
sorafenib
Anorexia
Exanthema
Platinum
Protein-Tyrosine Kinases
Fatigue
Disease Progression
Weight Loss
Diarrhea
Maintenance

Keywords

  • Angiogenesis inhibitor
  • Small cell lung cancer
  • Sorafenib
  • VEGFR tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

Cite this

Phase II trial of Sorafenib in conjunction with chemotherapy and as maintenance therapy in extensive-stage small cell lung cancer. / Sharma, Neelesh; Pennell, Nathan; Nickolich, Myles; Halmos, Balazs; Ma, Patrick; Mekhail, Tarek; Fu, Pingfu; Dowlati, Afshin.

In: Investigational New Drugs, Vol. 32, No. 2, 2014, p. 362-368.

Research output: Contribution to journalArticle

Sharma, Neelesh ; Pennell, Nathan ; Nickolich, Myles ; Halmos, Balazs ; Ma, Patrick ; Mekhail, Tarek ; Fu, Pingfu ; Dowlati, Afshin. / Phase II trial of Sorafenib in conjunction with chemotherapy and as maintenance therapy in extensive-stage small cell lung cancer. In: Investigational New Drugs. 2014 ; Vol. 32, No. 2. pp. 362-368.
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