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A phase II single-arm study of induction chemotherapy with cisplatin and gemcitabine followed by concurrent cisplatin and gemcitabine with thoracic radiation for unresectable locally advanced non-small cell lung cancer.

ABSTRACT: OBJECTIVES:The aim of this study was to evaluate the efficacy and tolerability of the combination of cisplatin-gemcitabine with concurrent thoracic radiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC). METHODS:This was a phase II, multicenter, open-label, single-arm trial in treatment-naïve patients with stage IIIA and IIIB LA-NSCLC. After three induction cycles with gemcitabine 1250 mg/m(2) plus cisplatin 80 mg/m(2), two concurrent chemoradiotherapy cycles with gemcitabine 300 mg/m(2), cisplatin 80 mg/m(2), and radiotherapy (63 Gy) were administered. The primary endpoint was response rate after induction chemotherapy followed by concurrent chemoradiotherapy. Secondary endpoints included time to progressive disease (TtPD), overall survival (OS), and safety. RESULTS:Overall, 49 patients (median age 63.4 years; 73.5% male; Karnofsky performance status scores of 80, 85, 90, and 100 [16.3%, 2.0%, 49.0%, and 32.7%, respectively]; disease stage IIIA or IIIB 28.6% and 71.4%, respectively) were enrolled and treated. Response rate was 38.8% (95% confidence interval [CI] 25.2-53.8%). Median TtPD was 11.4 months (95% CI 9.4-12.9). Median OS was 21.8 months (95% CI 17.5-26.0), with 1- and 2-year survival rates of 70.8% and 43.7%, respectively. Overall, six patients discontinued from study treatment due to adverse events (AEs), of which two were serious AEs. The most relevant grade 3/4 AEs were neutropenia and thrombocytopenia in induction chemotherapy and chemoradiotherapy, and grade 3 events related to radiation in acute chemoradiotherapy, e.g. dysphagia, radiation pneumonitis, and radiation esophagitis. CONCLUSIONS:Induction chemotherapy followed by concurrent chemoradiotherapy with gemcitabine (300 mg/m(2)) and cisplatin was associated with acceptable toxicity. The observed median OS time was 21.8 months. Response evaluation was difficult as in many cases it was not possible to differentiate tumor progression from local radiofibrosis.

SUBMITTER: Driesen P

PROVIDER: S-EPMC3630482 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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A phase II single-arm study of induction chemotherapy with cisplatin and gemcitabine followed by concurrent cisplatin and gemcitabine with thoracic radiation for unresectable locally advanced non-small cell lung cancer.

Driesen Peter P Lambrechts Marc M Kraaij Kees K Soldatenkova Victoria V Chouaki Nadia N Colinet Benoit B

Therapeutic advances in medical oncology 20130501 3

<h4>Objectives</h4>The aim of this study was to evaluate the efficacy and tolerability of the combination of cisplatin-gemcitabine with concurrent thoracic radiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC).<h4>Methods</h4>This was a phase II, multicenter, open-label, single-arm trial in treatment-naïve patients with stage IIIA and IIIB LA-NSCLC. After three induction cycles with gemcitabine 1250 mg/m(2) plus cisplatin 80 mg/m(2), two concurrent chemoradiotherapy cycles with ...[more]

PMID: 23634194

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Project description:BackgroundThe standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC study. Although multiple Japanese phase II studies have shown high efficacy and tolerability of CRT with cisplatin plus S-1 (SP), no prospective study using durvalumab after SP-based CRT has been reported.ObjectivesWe conducted a multicenter phase II study of this approach, the interim analysis of which showed a high transition rate to durvalumab consolidation therapy. Here, we report the primary analysis results.DesignIn treatment-naïve LA-NSCLC, cisplatin (60 mg/m2, day 1) and S-1 (80-120 mg/body, days 1-14) were administered with two 4-week cycles with concurrent thoracic radiotherapy (60 Gy) followed by durvalumab (10 mg/kg) every 2 weeks for up to 1 year.MethodsThe primary endpoint was 1-year progression-free survival (PFS). The expected 1-year PFS and its lower limit of the 80% confidence interval (CI) were set as 63% and 47%, respectively, based on the results of TORG1018 study.ResultsIn all, 59 patients were enrolled, with 51 (86.4%) proceeding to durvalumab. The objective response rate throughout the study was 72.9% (95% CI: 59.7-83.6%). After median follow-up of 21.9 months, neither median PFS nor OS was reached. The 1-year PFS was 72.5% (80% CI: 64.2-79.2%, 95% CI: 59.1-82.2%), while the 1-year overall survival was 91.5% (95% CI: 80.8-96.4%). No grade 5 adverse events were observed throughout the study. The most common adverse event during the consolidation phase was pneumonitis (any grade, 78.4%; grade ⩾3, 2.0%). Eventually, 52.5% of patients completed 1-year durvalumab consolidation therapy from CRT initiation.ConclusionThis study of durvalumab after SP-based CRT met its primary endpoint and found a 1-year PFS of 73% from CRT initiation. This study provides the first prospective data on the prognosis and tolerability of durvalumab consolidation from the initiation of CRT.Trial registrationJapan Registry of Clinical Trials, jRCTs031190127, registered 1 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.

Project description:Recent studies have suggested the superiority of concomitant over sequential administration of chemotherapy and radiotherapy. Docetaxel and cisplatin have demonstrated efficacy in advanced non-small-cell lung cancer (NSCLC). This study evaluated the safety, toxicity, and antitumour activity of docetaxel/cisplatin with concurrent thoracic radiotherapy for patients with locally advanced NSCLC. Patients with locally advanced NSCLC (stage IIIA or IIIB), good performance status, age <or=75 years, and adequate organ function were eligible. Both docetaxel and cisplatin were given on days 1, 8, 29, and 36. Doses of docetaxel/cisplatin (mg m(-2)) in the phase I study portion were escalated as follows: 20/30, 25/30, 30/30, 30/35, 30/40, 35/40, 40/40, and 45/40. Beginning on day 1 of chemotherapy, thoracic radiotherapy was given at a total dose of 60 Gy with 2 Gy per fraction over 6 weeks. In the phase I portion, the maximum tolerated doses (MTD) among 33 patients were docetaxel 45 mg m(-2) and cisplatin 40 mg m(-2). The major dose-limiting toxicity (DLT) was radiation oesophagitis. The recommended doses (RDs) for the phase II study were docetaxel 40 mg m(-2) and cisplatin 40 mg m(-2). A total of 42 patients were entered in the phase II portion. Common toxicities were leukopenia, granulocytopenia, anaemia, and radiation oesophagitis, with frequencies of grade >or=3 toxicities of 71, 60, 24, and 19%, respectively. Toxicity was significant, but manageable according to the dose and schedule modifications. Dose intensities of docetaxel and cisplatin were 86 and 87%, respectively. Radiotherapy was completed without a delay in 67% of 42 patients. The overall response rate was 79% (95% confidence interval (CI), 66-91%). The median survival time was 23.4+ months with an overall survival rate of 76% at 1 year and 54% at 2 years. In conclusion, chemotherapy with cisplatin plus docetaxel given on days 1, 8, 29, and 36 and concurrent thoracic radiotherapy is efficacious and tolerated in patients with locally advanced NSCLC and should be evaluated in a phase III study.

Dataset Information

A phase II single-arm study of induction chemotherapy with cisplatin and gemcitabine followed by concurrent cisplatin and gemcitabine with thoracic radiation for unresectable locally advanced non-small cell lung cancer.

Publications

A phase II single-arm study of induction chemotherapy with cisplatin and gemcitabine followed by concurrent cisplatin and gemcitabine with thoracic radiation for unresectable locally advanced non-small cell lung cancer.

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