Phase II study of nab-paclitaxel + carboplatin for patients with non-small-cell lung cancer and interstitial lung disease.

Abstract

The prognosis of non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) is poor, and 5%-20% of those receiving chemotherapy experience ILD exacerbation. To evaluate the safety and efficacy of nab-paclitaxel plus carboplatin for NSCLC patients with ILD, we undertook a multicenter phase II study. Chemotherapy-naïve patients with advanced NSCLC and mild or moderate ILD received nab-paclitaxel (100 mg/m2 , days 1, 8, and 15) plus carboplatin (area under the curve = 6, day 1) every 3 weeks for 4 cycles (maximum, 6 cycles). Interstitial lung diseases were diagnosed based on criteria for fibrosing interstitial pneumonia. The primary endpoint was the prevalence of exacerbation-free ILD 28 days after completion of protocol treatment. Secondary endpoints were response rate, progression-free survival, overall survival, prevalence of exacerbation-free ILD, and toxicity. Ninety-four patients were enrolled, and 92 patients received any protocol treatment. Median age was 70 years, and 58% had nonsquamous histology. In the primary analysis, the prevalence of exacerbation-free ILD 28 days after protocol treatment was 95.7% (88/92; 90% confidence interval, 90.3-98.5), which met the primary endpoint. Response rate was 51% (95% confidence interval, 40%-62%). At the time of data cut-off, median progression-free survival was 6.2 months, and median overall survival was 15.4 months. The most common grade 3/4 adverse events were neutropenia (75%), leukopenia (53%), anemia (48%), and thrombocytopenia (20%). Two treatment-related deaths (1 each of pulmonary infection and ILD exacerbation) were observed. This study showed that a combination of nab-paclitaxel with carboplatin was tolerable in NSCLC patients with mild or moderate ILD in terms of safety. This study is registered at the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN 000012989).

• Authors: Hirotsugu Kenmotsu, Kiyotaka Yoh, Keita Mori, Akira Ono, Tomohisa Baba, Yutaka Fujiwara, Ou Yamaguchi, Ryo Ko, Hiroaki Okamoto, Nobuyuki Yamamoto, Takashi Ninomiya, Takashi Ogura, Terufumi Kato
• Journal: Cancer science (Cancer Sci) Vol. 110 Issue 12 Pg. 3738-3745 (Dec 2019) ISSN: 1349-7006 [Electronic] England
• PMID: 31608537 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

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

Topics

• Aged
• Aged, 80 and over
• Albumins (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboplatin (administration & dosage, adverse effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality)
• Female
• Humans
• Lung Diseases, Interstitial (complications, epidemiology)
• Lung Neoplasms (drug therapy, mortality)
• Male
• Middle Aged
• Paclitaxel (administration & dosage, adverse effects)
• Prospective Studies