Phase I/II study of carboplatin plus weekly nab-paclitaxel in patients aged ≥75 years with squamous-cell lung cancer: TORG1322.

Abstract

OBJECTIVES:

This phase I/II study assessed the efficacy and safety of combination therapy with carboplatin (CBDCA) and nab-paclitaxel (nab-PTX) in advanced elderly patients (aged ≥75 years) with advanced squamous cell lung cancer (SqCLC).

MATERIALS AND METHODS:

In this phase I study, the doses of carboplatin at an area under the curve (AUC) of 5 or 6 mg/mL/min on day 1 (levels 1 and 2, respectively) were administered along with weekly nab-PTX (100 mg/m2) on days 1, 8, and 15 every 4 weeks for up to 6 cycles using a modified 3 + 3 design. The primary endpoint for the phase II study was the 6-month progression-free survival (6 m PFS) rate.

RESULTS:

A total of 46 patients were enrolled in this study. Ten patients were enrolled in the phase I part. At dose level 1, 2/7 patients showed dose-limiting toxicities (DLTs) of grade 3 diarrhea and febrile neutropenia; at dose level 2, 1/3 patient exhibited grade 3 anorexia as a DLT. The recommended dose was determined to be level 2. Efficacy was then evaluated in 39 patients enrolled in a phase II study. The median number of cycles was 4 (range, 1-6), and the median follow-up time was 17.5 months (range, 5.6-28.9 months). The 6 m PFS rate was 59.4% (90% confidence interval [CI], 44.8%-71.4%), and the primary endpoint was met. The median overall survival time was 23.5 months (95% CI, 11.6-35.4), and the median PFS was 6.8 months (95% CI, 5.4-9.1). The response rate was 54%, and the disease control rate was 92%. Sixteen patients (41%) received immune checkpoint inhibitors post-study. Common grade 3 or 4 toxicities were neutropenia (61.5%), anemia (46.2%), thrombocytopenia (17.9%), and febrile neutropenia (15.4%).

CONCLUSION:

Combination chemotherapy consisting of CBDCA with weekly nab-PTX had a promising efficacy and acceptable toxicities in elderly patients (aged ≥75 years) with advanced SqCLC.

• Authors: Yoshitaka Zenke, Seiji Niho, Shigeki Umemura, Masashi Ishihara, Nobuhiko Seki, Naoyuki Nogami, Yukio Hosomi, Tsuneo Shimokawa, Takaaki Tokito, Yasushi Goto, Yosuke Miura, Haruhiro Saito, Naoya Hida, Satoshi Ikeda, Hiroshi Tanaka, Naoki Furuya, Toshihiro Misumi, Takeharu Yamanaka, Yuichiro Ohe, Hiroaki Okamoto
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 146 Pg. 182-188 (08 2020) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 32559454 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

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

Topics

• Aged
• Albumins
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Carboplatin (therapeutic use)
• Carcinoma, Squamous Cell
• Humans
• Lung Neoplasms (drug therapy)
• Paclitaxel (adverse effects)