A Randomized, Phase II Trial of Two Dose Levels of Temsirolimus (CCI-779) in Patients With Extensive-Stage Small-Cell Lung Cancer Who Have Responding or Stable Disease After Induction Chemotherapy: A Trial of the Eastern Cooperative Oncology Group (E1500)

J Thorac Oncol. 2007 Nov;2(11):1036-41. doi: 10.1097/JTO.0b013e318155a439.

Abstract

Hypothesis: To study the progression-free survival (PFS) and toxicity with 25- or 250-mg doses of temsirolimus (CCI-779) after induction chemotherapy in patients with extensive small-cell lung cancer.

Methods: Patients with either stable or responding disease to four to six cycles of cisplatin or carboplatin plus etoposide or irinotecan were randomized between 4 and 8 weeks after completion of induction therapy to receive either 25 or 250 mg of temsirolimus intravenously every week until disease progression.

Results: Eighty-seven patients entered between January 2002 and December 2003, of whom 85 were eligible: 44 received 25 mg (arm A), and 41 received 250 mg (arm B). The overall median follow-up time for all eligible patients was 34.6 months. Median age was 59 years (range, 39-80); 42 (49.4%) were male and 43 (50.6%) female; 12.9% had brain metastases. The overall median and 1-year PFS were 2.2 months (95% confidence interval [CI]: 1.8, 2.9) and 4.7% (95% CI: 0.2%, 9.2%), respectively. The median PFS (95% CI) for arm A was 1.9 months (1.6, 2.3); for arm B, it was 2.5 months (1.9, 3.4; p = 0.24). The median overall survival from randomization was 8 months (95% CI: 6.5, 9.5). Among the 86 patients with reported toxicities, 36 (42%) had grade 3 toxicities, the most common of which were thrombocytopenia, hypophosphatemia, and fatigue, and an additional 12 (14%) had grade 4 toxicities, the most common of which was neutropenia. No patients experienced lethal toxicities.

Conclusion: Temsirolimus (CCI 779), given at 25 or 250 mg weekly, seemed not to increase the PFS in this patient population.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Carcinoma, Small Cell / drug therapy*
  • Carcinoma, Small Cell / pathology
  • Cisplatin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Irinotecan
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Protein Kinase Inhibitors / administration & dosage*
  • Remission Induction
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • Survival Rate
  • Treatment Outcome

Substances

  • Protein Kinase Inhibitors
  • temsirolimus
  • Etoposide
  • Irinotecan
  • Cisplatin
  • Sirolimus
  • Camptothecin