Phase I-II trial of concomitant continuous carboplatin (CBDCA) infusion and radiotherapy in advanced nonsmall cell lung cancer with evaluation for surgery: final report.
OBJECTIVE
The goal of this trial was to determine the maximum tolerable dose when carboplatin (CBDCA) was administered in continuous infusion concurrently with radiotherapy in patients with nonsmall cell lung cancer.


METHODS
From October 1989 to July 1993, 54 patients were studied (male/female ratio: 44 to 10), median age was 62 years. Two patients had Stage II cancer, 22 had Stage IIIA, 24 had Stage IIIB, and 6 had Stage IV. Carboplatin was given for 96 h, starting at a dose of 30 mg/m2/day: 13 patients received 30 mg/m2/day (group A), 12 patients received 50 mg/m2/day (group B), 12 patients received 70 mg/m2/day (group C), 10 patients received 90 mg/m2/day (group D), and 7 patients 110 mg/m2/day (group E). The radiation dose was 50.40 Gy delivered to the target volume in 5.3 weeks.


RESULTS
Fifty-three of 54 patients were evaluable for toxicity and 52 out of 54 for response. Toxicity (Miller score): Myelotoxicity: in groups A and B it was almost absent; in groups C and D it was moderate (leukopenia G1-2: 45.4% patients; trombocytopenia G1-2: 22.7%, G3: 9%; anemia G1-2: 9%); only in group E was it severe (leukopenia G1 and G3 16.6% respectively; trombocytopenia G3: 33.3%, G4: 16.6%; anemia G1-2: 50%). Nephrotoxicity was present only in one patient of group E and was Grade 3. Nausea and vomiting were related to CBDCA dose. One patient in Group E died of intractable toxicity 3 days after the end of infusion; then the study was closed. The limiting toxicity dose was shown to be 110 mg/m2/day given for 96 h. Clinical response rate: Twenty-six of 52 patients had major response, 24 had minor response, and only 2 patients had progression of disease.


METHODS
Twenty-one of 52 tumors were judged resectable: 18 patients had complete tumor resection, 1 had exploratory thoracotomy, and 2 patients refused surgery. Pathological response rate: Five patients had pathologic state T0 or Tis.


CONCLUSIONS
These results indicate that the maximum tolerable dose of CBDCA infusion for 96 h is 90 mg/m2/day, and this schedule seems to produce an appreciable response rate. Therefore, we have started a Phase II trial, which will permit us to define the true efficacy of this schedule.
Trodella
L
L
Department of Radiology, Catholic University, Rome, Italy.
Cellini
N
N
Picciocchi
A
A
Marano
P
P
Balducci
M
M
Mantini
G
G
Turriziani
A
A
Corbo
G M
GM
Valente
S
S
Valentini
V
V
Pirronti
T
T
Granone
P
P
Dobelbower
R R
RR
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced
D000970:Antineoplastic Agents; D016190:Carboplatin