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).
OBJECTIVE
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.


CONCLUSIONS
Temsirolimus (CCI 779), given at 25 or 250 mg weekly, seemed not to increase the PFS in this patient population.
Pandya
Kishan J
KJ
James P. Wilmot Cancer Center, University of Rochester, Rochester, New York 14642, USA. kishan_pandya@urmc.rochester.edu
Dahlberg
Suzanne
S
Hidalgo
Manuel
M
Cohen
Roger B
RB
Lee
Martin W
MW
Schiller
Joan H
JH
Johnson
David H
DH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D012074:Remission Induction; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015996:Survival Rate; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D005047:Etoposide; D000077146:Irinotecan; D002945:Cisplatin; D020123:Sirolimus; D002166:Camptothecin