Combined modality therapy in non-small cell lung cancer

Purpose In 699 patients with locally advanced non–small-cell lung cancer (NSCLC) treated with radiation therapy as part of combined modality therapy, we compared outcomes among genotyped and ungenotyped patients and by tumor genotype status ( EGFR, KRAS, and ALK). Patients and Methods Genotyping was performed in 250 patients: EGFR+ (19%), KRAS+ (32%), ALK+ (9%), and wild type (WT−/−/−; 40%). Outcomes were analyzed using the Kaplan-Meier method and Cox regression. Results With a median follow-up of 48.2 months among genotyped patients, median overall survival (OS) was significantly longer for EGFR+ and ALK+ compared with KRAS+ and WT−/−/− (55.8 months v not reached v 28.0 v 33.2 months; P = .02). There was no difference in progression-free survival (median, 15.3 v 13.7 v 13.0 v 14.5 months; P = .47) or in freedom from distant metastases by genotype (3-year estimates: 42% v 49% v 27% v 25%; P = .25). There was higher freedom from locoregional recurrence (LRR) for EGFR+ tumors and lower freedom from LRR in ALK+ tumors, compared with KRAS+ and WT−/−/− tumors (3-year: 77% v 38% v 49% v 46%). In multivariable analysis, ALK+ remained associated with increased OS (HR, 0.32; 95% CI, 0.12 to 0.87; P = .03), and EGFR+ was associated with decreased LRR (HR, 0.47; 95% CI, 0.24 to 0.92; P = .03). Analysis of post-recurrence survival demonstrated that EGFR+/ ALK+ patients treated with appropriate tyrosine kinase inhibitors had higher OS compared with other groups. Conclusion In this series of locally advanced NSCLC treated with combined modality therapy, EGFR+ and ALK+ were associated with higher OS, whereas LRR was lower in EGFR+ patients, and the risk of distant metastases was high in all subgroups. The outcomes and patterns of failure in genotypic subgroups of NSCLC from this study can inform the design of future trials integrating targeted therapies.

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Paclitaxel in combination chemotherapy with radiotherapy in patients with unresectable stage III non-small-cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.5.1642 ◽

1996 ◽

Vol 14 (5) ◽

pp. 1642-1648 ◽

Cited By ~ 22

Author(s):

F A Greco ◽

S L Stroup ◽

J R Gray ◽

J D Hainsworth

Keyword(s):

Lung Cancer ◽

Radiation Therapy ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Combined Modality Therapy ◽

Small Cell ◽

Stage Iii ◽

Small Cell Lung ◽

Combined Modality ◽

Grade 3

PURPOSE The addition of combination chemotherapy to standard radiation therapy has improved treatment for locally unresectable non-small-cell lung cancer. In this phase II study, we evaluated the toxicity and efficacy of a novel chemotherapy regimen that included paclitaxel, cisplatin, and etoposide plus concurrent radiation therapy in this group of patients. PATIENTS AND METHODS Thirty-three patients with previously untreated, unresectable stage III non-small-cell lung cancer (stage IIIA, 11 patients; stage IIIB, 22 patients) initially received two courses of chemotherapy, which included paclitaxel 135 mg/m2 by 1-hour infusion on day 1, cisplatin 60 mg/m/ intravenously (i.v.) on day 2, and etoposide 100 mg/m2 i.v. on days 1, 2 and 3. On week 6, radiation therapy (60 Gy in 30 fractions) was initiated in conjunction with two additional courses of chemotherapy: paclitaxel 135 mg/m2 i.v. by 1-hour infusion on day 1, cisplatin 5 mg/m2 i.v. on days 2- to 10, and etoposide 25 mg/m2 on days 1 to 10. RESULTS This combined modality program was feasible and well tolerated by most patients. During the two courses of induction chemotherapy, grade 3 or 4 myelosuppression occurred in only six patients (18%). Esophagitis was common during combined modality therapy (grade 3, 10 patients; grade 4 five patients). Forty-two percent of patients had partial response after two courses of induction therapy, and 82% of patients had an objective response at completion of therapy. Twelve patients (36%) had a complete response. Nineteen patients remain progression-free at a median of 8 months; the median survival time has not been reached. CONCLUSION This paclitaxel-containing combined modality therapy is feasible and highly active in patients with inoperable stage III lung cancer. Esophagitis is the most common severe toxicity with this program. Further studies with paclitaxel-containing combination regimens in patients with stage III non-small-cell lung cancer are indicated.

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