A phase I study of the tyrosine kinase inhibitor anlotinib combined with platinum/pemetrexed-based chemotherapy in untreated nonsquamous non-small-cell lung cancer

SummaryBackground. Anlotinib hydrochloride is an oral small molecule inhibitor of multiple tyrosine kinases, and it has been approved as a third-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) in China. This dose-exploration study was designed to investigate the feasibility of anlotinib in combination with other chemotherapy regimens in patients with nonsquamous NSCLC. Methods. This phase I study followed a 3 + 3 dose reduction design with three doses of anlotinib (12 mg, 10 mg, and 8 mg). Anlotinib was given at an initial dose of 12 mg with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC = 5) on 21-day cycles for 4 cycles. The primary goal of the study was to identify the maximum tolerated dose (MTD), and secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results. A total of eight participants were enrolled. Dose-limiting toxicities (DLTs) were observed in two patients (pts) at anlotinib 12 mg (grade 3 hand-foot syndrome and grade 3 appetite loss). No DLTs occurred with 10 mg anlotinib, and the MTD was 10 mg. Among seven evaluable pts, four achieved a confirmed partial response (PR), and three had stable disease (SD). With a median follow-up of 10.05 months, the median PFS was 7.00 months (95% CI: 2.76 to NE). Grade 3 treatment-related adverse events (TRAEs) included appetite loss (n = 2), hypertension (n = 2), thrombocytopenia (n = 1), diarrhea (n = 1) and hand-foot syndrome (n = 1). No grade 4 or grade 5 TRAEs were observed during the treatment. Conclusion. The feasible dose of anlotinib in combination with platinum/pemetrexed-based chemotherapy as a first-line regimen was 10 mg, which was well tolerated and showed promising antitumor activity in advanced nonsquamous NSCLC.

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A phase I study of anlotinib combined with platinum-pemetrexed in untreated non-squamous non-small cell lung cancer

10.21203/rs.3.rs-698041/v1 ◽

2021 ◽

Author(s):

Meijuan Huang ◽

Yong-mei Liu ◽

Min Yu ◽

Yan-ying Li ◽

Yan Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Phase I ◽

Small Cell Lung Cancer ◽

Phase I Study ◽

Small Cell ◽

Small Cell Lung ◽

Appetite Loss ◽

Line Therapy ◽

Hand Foot Syndrome ◽

Grade 3

Abstract Background Anlotinib hydrochloride is an oral small molecule multi-target tyrosine kinase inhibitor, and it has been approved as third-line therapy for patients with advanced non-small cell lung cancer (NSCLC) in China. This dose-exploration study was designed to investigate the feasibility of anlotinib in combination with chemotherapy in patients with non-squamous NSCLC. Methods This phase I study followed a 3 + 3 dose reduction design with three dose levels of anlotinib (12mg, 10mg, 8mg). Anlotinib was given at an initial dose of 12mg with pemetrexed (500mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC = 5) on 21-day cycles for 4 cycles. The primary goal of the study was to identify the maximum tolerated dose (MTD) and secondary endpoints included progression free survival (PFS) and overall survival (OS). Results A total of eight participants were enrolled. DLTs were observed in two patients (pts) at anlotinib 12mg (grade 3 hand-foot syndrome and grade 3 appetite loss). No DLTs occurred at anlotinib 10mg and the MTD was 10mg. Among seven pts evaluable, four achieved confirmed partial response (PR) and three had stable disease (SD). With a median follow-up of 10.05 months, the median PFS was 7.00 months (95%CI: 2.76 to NE). Grade 3 treatment-related adverse events (TRAEs) included appetite loss (n = 2), hypertension (n = 2), thrombocytopenia (n = 1), diarrhea (n = 1) and hand-foot syndrome (n = 1). No grade 4 or grade 5 TRAEs observed during the treatment. Conclusion The feasible dose of anlotinib in combination with platinum-pemetrexed as first-line therapy was 10 mg, which was well tolerated and showed promising antitumor activity in advanced non-squamous NSCLC.

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Phase I/II study of amrubicin and nedaplatin in patients with untreated, advanced non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.7569 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 7569-7569

Author(s):

Hiroaki Senju ◽

Daiki Ogawara ◽

Yoichi Nakamura ◽

Minoru Fukuda ◽

Katsumi Nakatomi ◽

...

Keyword(s):

Lung Cancer ◽

Phase I ◽

Small Cell Lung Cancer ◽

Dose Level ◽

Cell Lung Cancer ◽

Phase I Study ◽

Maximum Tolerated Dose ◽

Small Cell ◽

Small Cell Lung ◽

Grade 3

7569 Background: We conducted a phase I/II study of combination chemotherapy with nedaplatin (CDGP) and amrubicin (Amr) for patients with untreated, advanced non small-cell lung cancer (NSCLC). Methods: Eligible patients were having adequate organ function and PS of 0-1. CDGP was given on day 1 and amrubicin on days 1, 2 and 3. The treatment was repeated every 3 weeks. We fixed the dose of CDGP as 100 mg/m2, and escalated the dose of amrubicin from a starting dose of 25 mg/m2 by 5mg/m2 per each levels until the maximum tolerated dose (MTD). The MTD was defined as the dose level at which at least two of three or two of six patients experienced a dose-limiting toxicity (DLT). Results: Between June 2009 and May 2011, 36 patients were enrolled. In the phase I study, two DLTs occurred in six patients at level 2; dose level 1 was therefore recommended (25 mg/m2 Amr, 100mg/m2 CDGP). DLTs included cerebral infarction and grade 4 thrombocytopenia. In the phase II study, including phase I study, a total of 36 patients were enrolled and 132 cycles of chemotherapy were conducted. Grade 3 or 4 neutropenia, grade 3 anemia and grade 3 or 4 thrombocytopenia occurred in 75%, 16.6% and 19.4% in all cycles, respectively. Febrile neutropenia occurred in 4cycles (3%) but all of them were controllable. Eighteen patients achieved a partial response and the overall response rate was 51.4%. Conclusions: Combination of CDGP and Amr was highly effective and well tolerable in patients with untreated, advanced NSCLC.

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Phase I study of concurrent and consolidation cisplatin and docetaxel chemotherapy with thoracic radiotherapy in non-small cell lung cancer

Current Oncology ◽

10.3747/co.25.3657 ◽

2018 ◽

Vol 25 (1) ◽

pp. 22

Author(s):

T.W. Zhang ◽

G.B. Rodrigues ◽

A.V. Louie ◽

D. Palma ◽

A.R. Dar ◽

...

Keyword(s):

Lung Cancer ◽

Phase I ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Phase I Study ◽

Small Cell ◽

Thoracic Radiotherapy ◽

Small Cell Lung ◽

Unresectable Stage ◽

Grade 3

Background We designed a phase i study of concurrent chemoradiotherapy (ccrt) with docetaxel (D) and cisplatin (C), followed by consolidation dc, for unresectable stage iii non-small cell lung cancer (nsclc).Methods Patients with histologically proven and unresectable stage iii nsclc were eligible. During ccrt, C was given every 3 weeks (75 mg/m2) and D given weekly. The starting dose of D was 20 mg/m2, escalated in cohorts of 3 to define the maximum tolerated dose (mtd). Radiotherapy was prescribed to a dose of 60 Gy in 30 fractions. This was followed by 2 cycles of consolidation dc, which were dose escalated if ccrt was tolerated.Results Twenty-six patients were enrolled, with 1 excluded following evidence of metastatic disease. Nineteen patients completed both phases of treatment. There were 7 grade 3 events during ccrt (5 esophagitis, 2 nausea), and 8 grade 3 events during consolidation (2 neutropenia, 2 leukopenia, 1 esophagitis, 2 nausea, and 1 pneumonitis). Three patients had grade 4 neutropenia. No patients died due to toxicities. The mtd of concurrent weekly D was 20 mg/m2. Consolidation D and C were each dose escalated to 75 mg/m2 in 8 patients. The median overall survival (os) and progression-free survival (pfs) of all patients were 33.6 months and 17.2 months, respectively, with median follow-up of 26.6 months (range 0.43–110.8).Conclusions The use of docetaxel 20 mg/m2 weekly and cisplatin 75 mg/m2 every 3 weeks concurrent with thoracic radiotherapy, followed by consolidation docetaxel and cisplatin, both given at 75 mg/m2 every 3 weeks, appears to be safe in this phase i trial.

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