A Phase I/II Study of Biweekly Carboplatin and Nab-paclitaxel With Concurrent Radiotherapy for Patients With Locally Advanced Unresectable Stage III Non-small-cell Lung Cancer

Clin Lung Cancer. 2021 Jan;22(1):42-48. doi: 10.1016/j.cllc.2020.09.016. Epub 2020 Oct 14.

Abstract

Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with locally advanced non-small-cell lung cell cancer (LA-NSCLC). We conducted a phase I/II study of biweekly carboplatin and nab-paclitaxel (nab-PTX) with radiotherapy (RT).

Materials and methods: In the phase I part, patients with inoperable stage IIIA/IIIB NSCLC were treated with carboplatin (area under the time-concentration curve, 4) and nab-PTX (60-100 mg/m2) on days 1, 15, and 29. Thoracic RT was administered from day 1 to a total dose of 60 Gy in 30 fractions. In the phase II part, patients were administered carboplatin and nab-PTX on days 1, 15, and 29 at the recommended dose (RD). The primary endpoint of the phase I part was to determine the maximum tolerated dose and the RD. In the phase II part, the primary endpoint was 2-year overall survival (OS) rate, and secondary endpoints were the objective response rate, progression-free survival, OS, and safety profile.

Results: In the phase I part, although maximum tolerated dose was not obtained, the RD was carboplatin (area under the time-concentration curve, 4) and nab-PTX (100 mg/m2). Of the evaluable 28 patients, the rate of 2-year OS was 67.8% (95% confidence interval, 49.3%-82.1%). The objective response rate was 96.4%, and the median follow-up time was 33.2 months. The median progression-free survival was 18.2 months (95% confidence interval, 13.1 months to not reached). The most common toxicities of grade 3 or higher were neutropenia (60.5%), anemia (14.2%), thrombocytopenia (7.2%), and pneumonitis (3.6%).

Conclusions: This study achieved the primary endpoint. Biweekly carboplatin and nab-PTX with concurrent RT was well-tolerated and exerted promising antitumor activity.

Keywords: Biweekly; Carboplatin; Concurrent chemoradiotherapy; Nanoparticles albumin-bound paclitaxel; Non–small-cell lung carcinoma.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adenocarcinoma of Lung / pathology
  • Adenocarcinoma of Lung / therapy*
  • Adult
  • Aged
  • Albumins / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy / methods*
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Young Adult

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Carboplatin
  • Paclitaxel