Late intensification chemotherapy with autologous bone marrow transplantation in selected small-cell carcinoma of the lung: a randomized study.
A multicentric randomized prospective trial was conducted to test whether late intensification chemotherapy would increase the remission rate, the relapse-free survival, and the survival of small-cell lung cancer patients responding to induction chemotherapy. Autologous bone marrow transplantation was used as support to reduce the duration of the aplasia induced by very high-dose chemotherapy. As induction chemotherapy, 101 patients received, during a period of 5 months, a total dosage of 120 mg/m2 methotrexate, 4.5 mg/m2 vincristine, 1,800 mg/m2 cyclophosphamide, 180 mg/m2 doxorubicin, 160 mg/m2 cisplatin, 750 mg/m2 VP-16-213, and 30 Gy prophylactic cranial irradiation. Forty-five patients, selected for their sensitivity to this induction treatment, were randomized to a last cycle of chemotherapy that combined cyclophosphamide, BCNU, and VP-16-213 either at a conventional dosage of 750 mg/m2 intravenously (IV), 60 mg/m2 IV, and 600 mg/m2 orally or alternatively at a very high dosage of 6 g/m2 IV, 300 mg/m2 IV, and 500 mg/m2 IV, respectively. In the late intensification group, the complete remission rate increased from 39% before randomization to 79% after high-dose chemotherapy. Median relapse-free survivals after randomization for intensified and control chemotherapy groups were 28 and 10 weeks, respectively (P = .002). Median overall survival after induction therapy was 68 weeks for the intensified group compared with 55 weeks for the conventional therapy group (P = .13). Four patients died during intensification. Patients in both groups relapsed at the primary site. It can thus be concluded that late intensification chemotherapy for sensitive small-cell lung cancer increases the complete remission rate and resulted in a statistically significant increase in the relapse-free survival. However, since relapse occurred at the primary site and toxicity was high, overall survival was not significantly improved.
Humblet
Y
Y
Ludwig Institute for Cancer Research, Brussels, Belgium.
Symann
M
M
Bosly
A
A
Delaunois
L
L
Francis
C
C
Machiels
J
J
Beauduin
M
M
Doyen
C
C
Weynants
P
P
Longueville
J
J
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011446:Prospective Studies / Q000009:adverse effects; D011897:Random Allocation; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D003520:Cyclophosphamide; D008727:Methotrexate