A prospective phase II study: high-dose pemetrexed as second-line chemotherapy in small-cell lung cancer.
OBJECTIVE
To investigate the efficacy and tolerability of high-dose pemetrexed as second-line chemotherapy in small cell lung cancer (SCLC).


METHODS
Patients with verified SCLC who had received one prior chemotherapy regimen, aged 18-75 years, WHO Performance Status 0-2, no clinical signs of brain metastases and measurable disease were eligible. Patients received pemetrexed 900 mg/m(2) IV every 3 weeks. Four courses were planned for all patients. Patients with relapse later than 3 months since last course of first-line chemotherapy were defined as "sensitive", those with relapse within 3 months as "refractory". Toxicity was graded using the CTCAE v3.0.


RESULTS
36 patients were accrued, 34 received study treatment. Median age was 61 (range 43-74), 18 (53%) males and 16 (47%) females. Mean number of courses administered was 2.5. One patient (3%) had partial response, three (9%) had stable disease and 29 (85%) progressed. One patient (3%) was not evaluable for response. Median TTP (n=33) was 7.7 weeks ("sensitive": 8.4 weeks, "refractory": 5.1 weeks). Median OS (n=34) was 17.6 weeks ("sensitive": 22.6 weeks, "refractory": 15.3 weeks). Of grade 3-4 haematological toxicity, anemia was observed in 2 (6%) patients, leukopenia in 6 (18%), granulocytopenia in 9 (27%) and thrombocytopenia in 3 (9%). Febrile neutropenia occurred in 6 (18%) patients. There were no treatment related deaths.


CONCLUSIONS
High-dose pemetrexed monotherapy to patients with recurrent SCLC yielded moderate toxicity, but limited treatment efficacy.
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NO-7491 Trondheim, Norway. bhgr@hotmail.com
Bjørn H
BH
Grønberg
Roy M
RM
Bremnes
Ulf
U
Aasebø
Paal
P
Brunsvig
Oystein
O
Fløtten
Tore
T
Amundsen
Christian
C
von Plessen
Mari
M
Wang
Stein
S
Sundstrøm
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D011446:Prospective Studies; D012008:Recurrence; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine