Platinum-etoposide chemotherapy in elderly patients with small-cell lung cancer: results of a randomized multicenter phase II study assessing attenuated-dose or full-dose with lenograstim prophylaxis--a Forza Operativa Nazionale Italiana Carcinoma Polmonare and Gruppo Studio Tumori Polmonari Veneto (FONICAP-GSTPV) study.
OBJECTIVE
Small-cell lung cancer (SCLC) is increasingly diagnosed in elderly patients, who are at higher risk of treatment-related morbidity and mortality. We conducted a randomized two-stage phase II study to assess the therapeutic index of two different platinum/etoposide regimens, attenuated-dose (AD) and full-dose (FD) plus prophylactic lenograstim.


METHODS
SCLC patients older than 70 years were randomized to receive four courses of cisplatin 25 mg/m(2) on days 1 and 2, and etoposide 60 mg/m(2) on days 1, 2, and 3 every 3 weeks (AD); or cisplatin 40 mg/m(2) on days 1 and 2, and etoposide 100 mg/m(2) on days 1, 2, and 3 every 3 weeks, plus lenograstim 5 mg/kg days 5 through 12, every 3 weeks (FD). A combined primary end point named therapeutic success (TS), which took into account activity, toxicity, and compliance, was used.


RESULTS
Ninety-five patients were enrolled. Seventy-five percent and 72% of the patients in the AD and FD arms, respectively, completed the treatment as per protocol. Response rate was 39% and 69% in the AD and FD arms, respectively, and 1-year survival probability was 18% and 39%, respectively. Treatment was well tolerated in both groups, with no grade 3 to 4 myelotoxicity in the AD arm, and 12% myelotoxicity in the FD arm. Overall, the observed TSs were 10 (36%) of 28 patients and 42 (63%) of 67 patients for AD and FD treatments, respectively.


CONCLUSIONS
In elderly patients with SCLC a full-dose cisplatin/etoposide regimen combined with prophylactic lenograstim is active and feasible, while attenuated doses of the same regimen are associated with a poor therapeutic outcome.
Ardizzoni
Andrea
A
Medical Oncology, Parma University Hospital, Via Gramsci 14, 43100 Parma, Italy. aardizzoni@ao.pr.it
Favaretto
Adolfo
A
Boni
Luca
L
Baldini
Editta
E
Castiglioni
Federico
F
Antonelli
Paola
P
Pari
Franca
F
Tibaldi
Carmelo
C
Altieri
Alfonso M
AM
Barbera
Sante
S
Cacciani
Giancarlo
G
Raimondi
Mario
M
Tixi
Lucia
L
Stefani
Micaela
M
Monfardini
Silvio
S
Antilli
Antonio
A
Rosso
Riccardo
R
Paccagnella
Adriano
A
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D000078224:Lenograstim; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage; D016896:Treatment Outcome
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D000078224:Lenograstim; D002945:Cisplatin