Dose-escalation study of pemetrexed in combination with carboplatin followed by pemetrexed maintenance therapy for advanced non-small cell lung cancer

Okamoto, Isamu; Takeda, Koji; Daga, Haruko; Miyazaki, Masaki; Yonesaka, Kimio; Kiyota, Hidemi; Tsurutani, Junji; Ueda, Shinya; Ichikawa, Yasuko; Takeda, Masayuki; Sekiguchi, Risa; Tominaga, K; Enatsu, Sotaro; Nambu, Yoshihiro; Nakagawa, Kazuhiko

doi:10.1016/j.lungcan.2010.02.007

Cited by 11 publications

(15 citation statements)

References 17 publications

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“…Multiple studies demonstrated that the utility of extrapolating the Calvert formula in calculating the dosage of carboplatin was better than the calculation method according to the body surface area, as it takes into account individual differences in renal function . In the previous study, different carboplatin doses (AUC 5 or 6) were used of the pemetrexed (500 mg/m 2 ) and carboplatin combination regimen as the first‐line treatment for Japanese patients with advanced non‐squamous NSCLC, and the results showed that ORR were 66.7% and 57.1% for the AUC 5 ( n = 6) and 6 ( n = 14) groups, respectively . Another study of a Japanese population of pemetrexed (500 mg/m 2 ) and carboplatin treatment for elderly (aged ≥75 years) untreated patients ( n = 17) with advanced non‐squamous NSCLC showed that ORR were 33.3%, 57.1%, and 42.9% for the AUC 4, 5, and 6 groups, respectively .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of calculating carboplatin dosage in carboplatin–pemetrexed therapy as the first‐line therapy for Chinese patients with advanced lung adenocarcinoma

et al. 2018

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ObjectiveThis study aims to explore the application of actual carboplatin in carboplatin plus pemetrexed regimen as first‐line treatment for advanced lung adenocarcinoma, and to determine the recommended dose of carboplatin for Chinese populations.MethodsFrom January 2014 to April 2016, 151 advanced lung adenocarcinoma patients who received carboplatin and pemetrexed (500 mg/m2) were included. The area under the curve (AUC) of carboplatin was back‐calculated from actual dosages using the Calvert formula. According to the median of calculated AUC, patients were divided into AUC ≥4 and <4 groups.ResultsThe median of AUC was 4 (1.8–5.5). A total of 79 patients had an AUC ≥4 and 72 patients had an AUC <4. The mean relative dose intensities of pemetrexed were 100.4% for the AUC ≥4 group, and 101.4% for <4 group. Baseline characteristic variables were balanced between the two groups, except for Eastern Cooperative Oncology Group Performance score (P = 0.044). The overall response rate (ORR) and disease control rate (DCR) were 33.8% and 90.1%, respectively, 35.4% and 86.1% for the AUC ≥4 group, and 31.9% and 94.4% for the AUC <4 group. No significant difference was observed in ORR (P = 0.650) and DCR (P = 0.086) between the two groups.ConclusionCompared with an AUC of 5 or 6, the actual clinical application of AUC was generally insufficient for Chinese populations; fortunately, therapeutic efficacy remained equal. We found that AUC <4 was as adequate as AUC ≥4 in pemetrexed plus carboplatin regimen as first‐line treatment for them.

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Section: Discussionmentioning

confidence: 99%

Evaluation of calculating carboplatin dosage in carboplatin–pemetrexed therapy as the first‐line therapy for Chinese patients with advanced lung adenocarcinoma

et al. 2018

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“…The MTD was not reached in the present study; nonetheless, carboplatin AUC 5 was finally determined as the RD because of the frequent occurrence of grade 3 hematological toxicities at this dose, such as neutropenia in 50% of the cases and thrombocytopenia in 67% of the cases in the level 3 cohort. In a previous study examining the use of carboplatin plus pemetrexed in younger patients (≤75 years old), the RD was determined to be AUC 6 for carboplatin and 500 mg/m 2 for pemetrexed because the incidences of hematological adverse events of grade ≥3 were 71% for neutropenia and 43% for thrombocytopenia [11]. In the present study, the incidence of high-grade thrombocytopenia of 67% in the level 3 cohort was higher than that in the aforementioned study in younger patients; therefore, we decided to set the RD at level 2.…”

Section: Discussionmentioning

confidence: 99%

Dose Escalation and Pharmacokinetic Study of Carboplatin plus Pemetrexed for Elderly Patients with Advanced Nonsquamous Non-Small-Cell Lung Cancer: Kumamoto Thoracic Oncology Study Group Trial 1002

et al. 2014

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Objectives: This study was designed to determine the recommended dose of carboplatin and pemetrexed for elderly (≥70-year-old) chemotherapy-naïve patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) and to investigate the pharmacokinetics of pemetrexed. Methods: The patients were treated with 4-6 cycles of carboplatin plus a fixed dose of pemetrexed (500 mg/m²) every 3 weeks; the dose of carboplatin was escalated [from area under the curve (AUC) 4 to AUC 6]. To examine the pharmacokinetics of pemetrexed, blood samples were collected before and after pemetrexed infusion, and the blood levels of pemetrexed were measured by liquid chromatography-mass spectrometry. Results: Grade 3 infection as a dose-limiting toxicity was observed at a carboplatin dose of AUC 6. We therefore determined a carboplatin dose of AUC 5 and a pemetrexed dose of 500 mg/m² as the recommended doses from this study. The pharmacokinetic study showed a significant inverse correlation between the AUC of pemetrexed and the creatinine clearance. Conclusions: For elderly chemotherapy-naïve patients with advanced nonsquamous NSCLC, the combination of carboplatin AUC 5 plus pemetrexed 500 mg/m² is recommended as a promising regimen; however, a reduction of the pemetrexed dose may be required for patients with renal dysfunction because of the high risk of hematotoxicities. © 2014 S. Karger AG, Basel

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“…Because carboplatinbased regimens have been shown to be less toxic, more convenient, they have been widely used as a substitute for cisplatin regimens in clinical practice, especially for elderly patients. In a previous dose escalation study of carboplatin plus pemetrexed for patients aged ,75 years with advanced NSCLC, this combination was shown to be effective and less toxic (14). However, the optimal doses of carboplatin and pemetrexed for patients aged 75 years with advanced non-sq NSCLC have not yet been fully evaluated.…”

Section: Introductionmentioning

confidence: 99%

“…For non-elderly patients, the recommended dose of this combination was carboplatin at an AUC of 6 and pemetrexed at 500 mg/m 2 , based on a previous dose escalation study (14). However, we did not plan to escalate that dose level in the present study for the following reasons: first, in the dose escalation study for non-elderly patients, hematological toxicities were more frequent for carboplatin at an AUC of 6 and pemetrexed at 500 mg/m 2 than for carboplatin at an AUC of 5 and pemetrexed at 500 mg/m 2 .…”

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confidence: 99%

Phase I Study of Carboplatin Combined with Pemetrexed for Elderly Patients with Advanced Non-squamous Non-small Cell Lung Cancer

Takeoka

Yamada

Azuma

et al. 2014

Japanese Journal of Clinical Oncology

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Objective: The primary objective of this study was to evaluate the safety and tolerability of carboplatin plus pemetrexed for elderly patients (75 years) with chemotherapy-naïve advanced non-squamous non-small cell lung cancer. Methods: Patients received escalated doses of carboplatin at an area under the concentration -time curve of 4 (Level 1) or 5 (Level 2) plus pemetrexed (500 mg/m 2 ) every 3 weeks for a maximum of six cycles. Dose escalation was decided according to whether dose-limiting toxicity occurred in the first cycle of chemotherapy. Results: A total of 20 patients (6 at Level 1, 14 at Level 2) were enrolled. No dose-limiting toxicities were observed in patients at Level 1 or the first six patients at Level 2, and therefore the combination of carboplatin at an area under the concentration -time curve of 5 plus pemetrexed at 500 mg/m 2 was considered to be the recommended dose. Among a total of 14 patients in Level 2, only 1 patient experienced dose-limiting toxicity: Grade 3 febrile neutropenia and urticaria. The major toxicities were neutropenia, thrombocytopenia and anemia. Liver dysfunction, fatigue and anorexia were also common, but generally manageable. Six patients showed partial responses, giving the overall response rate of 30%. The median progression-free survival period was 4.8 months (95% confidence interval 2.9-6.7 months). Conclusions: The combination of carboplatin at an area under the concentration -time curve of 5 plus pemetrexed at 500 mg/m 2 was determined as the recommended dose in chemotherapy-naïve elderly patients (75 years) with advanced non-squamous non-small cell lung cancer, in view of overall safety and tolerability.

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Dose-escalation study of pemetrexed in combination with carboplatin followed by pemetrexed maintenance therapy for advanced non-small cell lung cancer

Cited by 11 publications

References 17 publications

Evaluation of calculating carboplatin dosage in carboplatin–pemetrexed therapy as the first‐line therapy for Chinese patients with advanced lung adenocarcinoma

Evaluation of calculating carboplatin dosage in carboplatin–pemetrexed therapy as the first‐line therapy for Chinese patients with advanced lung adenocarcinoma

Dose Escalation and Pharmacokinetic Study of Carboplatin plus Pemetrexed for Elderly Patients with Advanced Nonsquamous Non-Small-Cell Lung Cancer: Kumamoto Thoracic Oncology Study Group Trial 1002

Phase I Study of Carboplatin Combined with Pemetrexed for Elderly Patients with Advanced Non-squamous Non-small Cell Lung Cancer

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