Long Term Follow-Up of Neoadjuvant-Adjuvant Combination Treatment of Iiia Stage Non-Small-Cell-Lung Cancer: Results of Neoadjuvant Carboplatin/Vinorelbine and Carboplatin/Paclitaxel Regimens Combined With Selective Adjuvant Chemotherapy According to in-Vitro Chemoresistance Test

Abstract

Aim:A prospective study investigated survival of patients with stage IIIA non-small-cell-lung cancer (NSCLC) treated with a combination of neoadjuvant and adjuvant chemotherapy.Methods: Consecutive chemo-naive patients with potentially operable stage IIIA NSCLC received carboplatin-based neoadjuvant treatment. Tumor cells harvested during surgery underwent methylthiazolyl tetrazolium blue (MTT) cytotoxic assay. After surgery, adjuvant chemotherapy was selected, where possible, according to MTT results.Results: A total of 65 patients were evaluated (31 received carboplatin/vinorelbine, 34 carboplatin/paclitaxel). The overall response rate was 67.7 % (95% confi dence interval [CI]: 56.3-79.1 %) with downstaging in 52.3 % (95% CI: 40.2-64.5 %) and no signifi cant diff erences between regimens. Median follow-up was 86 months: median overall survival (OS) was 32.1 months (95% CI: 7.4-46.5), median time to progression was 25.1 months (95% CI: 15.1-34.9 months) and fi ve-year overall survival was 35.7 % (95% CI: 23.7-47.7 %). Forty-seven patients (72.3 %) underwent surgery and 43 patients received adjuvant chemotherapy. Five-year survival after tumor resection was 49.5 % (95% CI: 34.2-64.8 %), median OS was 59.0 months (95% CI: 34.2-83.1) and median disease free survival after surgery was 57.3 months (95% CI: 29.5-84.4). With MTT-directed therapy, median OS was 85.1 months (95% CI: 15.4-148.6) and the 5-year survival rate was 57.0 % (95% CI: 34.5-79.5 %); the trend for longer survival failed to reach statistical signifi cance.Conclusions: A combination of carboplatin-based neoadjuvant chemotherapy, surgical resection and adjuvant chemotherapy achieved satisfactory survival rates in stage IIIA NSCLC, especially in patients with complete resection of tumor and those given MTT-directed adjuvant treatment. Our results suggest MTT testing may help optimise adjuvant chemotherapy.

Adjuvant Chemotherapy Based on the In Vitro Histoculture Drug Response Assay for Non-small Cell Lung Cancer Improves Survival

“…Several studies concerning chemosensitivity tests for lung cancer were previously reported. They used the MTT assay, 14 human tumor clonogenic assay, 15 HDRA, 13,16 differential staining toxicity assay, [17][18][19] adenosine triphosphate (ATP) assay, 20,21 extreme drug resistance assay, [22][23][24] and collagen droplet embedded culture drug sensitivity test (CD-DST). 25,26 Some studies indicated the clinical usefulness of chemosensitivity tests for lung cancer.…”

“…25,26 Some studies indicated the clinical usefulness of chemosensitivity tests for lung cancer. Kolek et al 14 reported that a combination of CBDCA-based neoadjuvant chemotherapy, surgical resection, and adjuvant chemotherapy achieved satisfactory survival rates in stage IIIA NSCLC, especially in patients with the complete resection of the tumor and those given MTT-directed adjuvant treatment and suggested that MTT testing may help optimize adjuvant chemotherapy. Moon et al 21 investigated correlations between the ATP assay and clinical outcomes after ATP assay-guided platinum-based chemotherapy in unresectable NSCLC.…”

Contemporary Trends of the Adjutant Chemotherapy in Non- small Cell Lung Cancer

“…Je možné také zmínit, že selektivní adjuvantní chemoterapii lze aplikovat na základě vyšetření in vitro rezistence nádorových buněk získaných při operaci. Provedená studie s dlouhodobým mediánem sledování ukázala trend k prodloužení přežití u takto podané chemoterapie [50]. Problémem tohoto přístupu je především náročné zpracovávání nádorových buněk a jejich nehomogenita.…”