Induction combination chemotherapy with docetaxel and carboplatin in advanced non-small-cell lung cancer.
BACKGROUND
Results in the therapy of locally advanced non-small-cell lung cancer (NSCLC) by operation and/or irradiation only are poor. To improve the long-term prognosis a systemic induction chemotherapy may be successful in reducing local tumor burden and eliminating micrometastases. The efficacy of preoperative docetaxel-carboplatin combination chemotherapy was studied in a phase-II study for NSCLC stage IIIB.


METHODS
15 patients with functionally operable stage IIIB NSCLC (10 squamous-cell, 4 adeno, 1 large-cell) were enrolled to receive 4 cycles of docetaxel (100 mg/m2, day 1) and carboplatin (AUC 7.5, day 2) on an outpatient basis with G-CSF support after cycle 1 and were subsequently evaluated for surgery. Postoperatively the patients were irradiated with 50 Gy (R0-resection) or 60 Gy (R1-resection).


RESULTS
Acceptable hematologic and non-hematologic toxicity was observed. On an intent-to-treat basis, 14 patients were evaluable for radiological response after 4 cycles of chemotherapy (1 patient still on therapy): 11/14 patients had radiological response of > or = 50%, 1/14 progressive disease, 2 exclusions because of toxic death (1 patient) and capillary leak (1 patient). Of 11 patients evaluated for surgery, 9 patients were resected, 1 patient is awaiting operation, 1 patient received radiotherapy because of an esophageal fistula. By histological findings a downstaging was achieved in 6/9 resected patients: histological complete response (CR) in 4 patients, partial response (PR) in 2, and no response in 3. With a mean follow-up of 8.1 months (excluding 1 patient in early postop course), 5/5 R0 and histological responders are alive and disease-free. Of the 3 histological non-responders, 1 patient (R1/2 resection) died of respiratory failure, 2 patients (1 R1 and 1 R0) of distant metastases.


CONCLUSIONS
Outpatient therapy with docetaxel/carboplatin chemotherapy is effective in downstaging patients with NSCLC, toxicity is acceptable. Histological response may be the most important prognostic factor. The early results of this phase II study encourage evaluation of the long-term benefit within a prospective randomized phase III study.
Herse
B
B
Department of Thoracic, Göttingen University, Germany.
Dalichau
H
H
Wörmann
B
B
Hemmerlein
B
B
Schmidberger
H
H
Hess
C F
CF
Hannemann
P
P
Criée
C P
CP
Hiddemann
W
W
Griesinger
F
F
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives; D043823:Taxoids; D013997:Time Factors; D016896:Treatment Outcome
D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D017239:Paclitaxel