Correlation of in vitro drug sensitivity testing results with response to chemotherapy and survival: comparison of non-small cell lung cancer and small cell lung cancer.
Clinical protocols for small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) were devised to prospectively select individualized chemotherapy based on in vitro drug sensitivity testing (DST) of cell lines derived from the patient's SCLC tumor cell lines or the patient's fresh NSCLC tumor. DST data derived from SCLC tumor cell lines were available for 33/115 (29%) patients. The DST-selected chemotherapy regimen was administered to 21 (18%) patients, or 64% of patients with DST. In SCLC< the DST-selected chemotherapy was administered either during weeks 13-24 following 12 weeks of etoposide/cisplatin, or at relapse after complete response to etoposide/cisplatin. Several parameters of in vitro drug sensitivity were significantly associated (two-sided P < 0.05) with clinical response to primary therapy and also with response to the DST-selected chemotherapy regimen, but were not associated with survival (P = 0.24). Five patients treated with their DST-selected chemotherapy attained a complete or partial response, compared to 5 of 68 who received an empiric regimen (P = 0.057). A total of 36/165 (22%) NSCLC patients had DST successfully completed. These results directed management for 21/96 (22%) patients who eventually received chemotherapy, or 58% of patients with DST. Response to chemotherapy for the patients treated prospectively with their DST-selected chemotherapy regimen (2/21; 9%) was not significantly different than the response rate for patients treated empirically with etoposide/cisplatin (10/69; 14%) in the absence of in vitro results to direct chemotherapy (P = 0.73). There was no difference in survival by treatment group for the NSCLC patients. The correlation between in vitro and clinical response was not significant for any individual drug or for all drugs considered together, illustrating the poor predictive value of in vitro testing with currently available chemotherapy in NSCLC.
Shaw
G L
GL
H. Lee Moffitt Cancer Center, University of South Florida, Tampa 33612, USA.
Gazdar
A F
AF
Phelps
R
R
Steinberg
S M
SM
Linnoila
R I
RI
Johnson
B E
BE
Oie
H K
HK
Russell
E K
EK
Ghosh
B C
BC
Pass
H I
HI
Minna
J D
JD
Mulshine
J L
JL
Ihde
D C
DC
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D002330:Carmustine / Q000494:pharmacology; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology; D005069:Evaluation Studies as Topic; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D008466:Mechlorethamine / Q000494:pharmacology; D008727:Methotrexate / Q000008:administration & dosage; D010166:Palliative Care; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013048:Specimen Handling; D016019:Survival Analysis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000008:administration & dosage / Q000494:pharmacology
D008466:Mechlorethamine; D014750:Vincristine; D005047:Etoposide; D008130:Lomustine; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D002330:Carmustine; D008727:Methotrexate