Outcomes of small-cell lung cancer patients treated with second-line chemotherapy: a multi-institutional retrospective analysis.
BACKGROUND
Patients with small-cell lung cancer (SCLC) that progress after first-line chemotherapy have a poor prognosis and the evidence of a benefit from second-line (SL) chemotherapy is limited. Patients relapsing or progressing more than 90 days after completion of first-line treatment are considered platinum sensitive and may be rechallenged with platinum-based chemotherapy. Topotecan is approved as SL treatment independent of time to progression. This retrospective analysis evaluates the clinical outcomes of SCLC patients who received SL chemotherapy after platinum-etoposide chemotherapy.


METHODS
We retrospectively reviewed 161 patients who received SL chemotherapy for SCLC. Patients were divided into four subgroups by type of SL treatment: (1) platinum-based rechallenge; (2) anthracycline-based regimens; (3) topotecan; (4) other single agents. The endpoints were overall survival (OS), progression-free survival (PFS) and response rate (RR). Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis to investigate factors influencing survival.


RESULTS
The median age was 63. There were 125 males and 36 females. Eastern Cooperative Oncology Group performance status (ECOG-PS) was 0, 1 and 2 in 12.5%, 62.5% and 25% of patients, respectively. Platinum sensitive/platinum resistant/platinum refractory/unknown=121/29/3/8 patients. Median time to SL chemotherapy was 6.9 months. The median PFS from starting second-line treatment was 4.3 months and median OS was 5.8 months. The overall RR was 22.9%. There was a trend toward higher RR (34.5% vs 17.5%, p for trend: 0.06) and OS (9.2 months vs 5.8 months, p=0.08) for patients with sensitive disease who were rechallenged with platinum-based chemotherapy. A multivariate analysis that adjusted for the time to SL treatment showed that a platinum-containing regimen achieves better RR, PFS and OS independently of the time to SL chemotherapy and that response to first-line treatment and PS at SL are the only independent prognostic factors.


CONCLUSIONS
The outcome for second-line therapy for SCLC was poor and benefit appeared to be limited to those patients with good PS and rechallenged with platinum-based chemotherapy. Platinum-based rechallenge should be considered as a standard comparator in future randomized controlled trials of SL chemotherapy.
Garassino
Marina Chiara
MC
Oncology Department, Ospedale Fatebenefratelli e Oftalmico, Milano, Italy.
Torri
Valter
V
Michetti
Giovanni
G
Lo Dico
Monica
M
La Verde
Nicla
N
Aglione
Stefania
S
Mancuso
Andrea
A
Gallerani
Elisa
E
Galetta
Domenico
D
Martelli
Olga
O
Collovà
Elena
E
Fatigoni
Sonia
S
Ghidini
Antonio
A
Saggia
Chiara
C
Bareggi
Claudia
C
Rossi
Antonio
A
Farina
Gabriella
G
Thatcher
Nicholas
N
Blackhall
Fiona
F
Lorigan
Paul
P
Califano
Raffaele
R
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010984:Platinum / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D016019:Survival Analysis; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D010984:Platinum; D005047:Etoposide; D019772:Topotecan