ABSTRACT
BACKGROUND/AIM: To assess the impact of drug selection upon the treatment of advanced and metastatic non-small cell lung cancer (NSCLC), we applied a functional platform that measures drug-induced cell death in human tumor primary-culture micro-spheroids isolated from surgical specimens. PATIENTS AND METHODS: At diagnosis, microspheroids isolated by mechanical and enzymatic disaggregation were examined for drug-induced cell-death by morphology and staining characteristics. Drugs were administered using standard protocols. Thirty-one patients, who received at least one cycle of therapy, were evaluable. All patients signed informed consent. RESULTS: Twenty out of 31 patients responded (64.5%), 1 completely and 19 partially, providing a two-fold improvement over historical control of 30% (p=0.00015), a median time-to-progression of 8.5 months and a median overall survival of 21.3 months. CONCLUSION: This functional platform is feasible and provides a favorable objective response rate, time-to-progression and survival in advanced, metastatic, untreated NSCLC, and warrants further evaluation.
Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Soft Tissue Neoplasms/drug therapy , Adrenal Gland Neoplasms/drug therapy , Adrenal Gland Neoplasms/secondary , Adult , Aged , Aged, 80 and over , Bone Neoplasms/drug therapy , Bone Neoplasms/secondary , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/secondary , Cell Death/drug effects , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Prognosis , Soft Tissue Neoplasms/secondary , Treatment Outcome , Tumor Cells, CulturedABSTRACT
PURPOSE: The combination of cisplatin plus gemcitabine is active in metastatic breast cancer. Carboplatin plus gemcitabine, widely used in ovarian and non-small-cell lung cancers, has also been used in breast cancer. This trial examined the efficacy and toxicity of split-dose carboplatin plus gemcitabine in advanced breast cancer. PATIENTS AND METHODS: Patients with measurable disease, recurrent after adjuvant and < or = 1 previous treatment for systemic disease, received carboplatin area under the curve = 2.0 (Calvert) plus gemcitabine 800 mg/m2, both drugs administered days 1 and 8 every 21 days. Of 15 patients accrued, 13 are fully evaluable. RESULTS: There were 2 complete (13.3%) and 6 partial (40%) responses, for an overall response rate by intention to treat of 53.3% (95% CI, 28%-82%). The median time to progression was 4.5 months (95% CI, 2.03-6.97 months), and median overall survival was 28.8 months (95% CI, 9.4-48.2 months). There were 2 patients with grade 3 (13.3%) anemia, 7 patients with grade 3 (46.6%) and 4 patients (26.6%) with grade 4 neutropenia, 4 patients with grade 3 (26.6%) and 3 patients (20%) with grade 4 thrombocytopenia. CONCLUSION: The repeating doublet of split-dose carboplatin plus gemcitabine reveals activity comparable to that of cisplatin plus gemcitabine, is well tolerated, and warrants evaluation in patients with recurrent breast cancer.
