High dose-intense chemotherapy alone or in combination with interleukin-2 for small cell lung cancer: a pilot study.
Given the antitumor activity of interleukin-2 (IL-2) against some drug-resistant cancer cells, 17 previously untreated patients with small cell lung cancer entered a pilot study to evaluate the feasibility, efficacy, and immunological effects of combining 12-week high dose-intense chemotherapy based on a modified Evans regimen (CAV/PE) with different IL-2 schedules (6-12 MU/m2 week as a 48-72-h infusion using the same cumulative dose, 72 MU/m2). Despite significant myelotoxicity, up to 70% of the intended dose intensity was delivered, showing no differences with regard to the IL-2 schedule used. Immunotherapy-induced toxicity was usually mild and manageable. No limiting effects were observed in patients receiving immunotherapy except for a very poor compliance to the 12-week IL-2 regimen. The low-dose 72-h infusion was the optimal IL-2 schedule. As given in this study, neither of the alternating CAV/PE regimens abrogated the effects of IL-2 on T-cell and NK-cell subsets, showing typical kinetics with rebound in lymphocytes following each discontinuation of the IL-2. While immunological changes cannot predict the antitumor effect of IL-2, they are consistent with those described for IL-2 alone, suggesting its compatibility with high dose-intense chemotherapy. Although no definite advantages have been demonstrated in this small pilot study with significant unbalanced prognostic factors (12% 2-year survival), both the preserved immunostimulatory effects and the lack of limiting overlapping toxicity make this combined approach promising and worthy of further clinical investigation.
Pollera
C F
CF
Division of Medical Oncology I, Istituto Regina Elena per lo Studio e la Cura dei Tumori, Rome, Italy.
Calabresi
F
F
Moreschi
M
M
Ruggeri
E M
EM
Giannarelli
D
D
Masciulli
R
R
Testa
U
U
Peschle
C
C
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D007376:Interleukin-2; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin