Tags

Type your tag names separated by a space and hit enter

Phase1 study of cisplatin plus pemetrexed with erlotinib and bevacizumab for chemotherapy-naïve advanced non-squamous non-small cell lung cancer with EGFR mutations.
Invest New Drugs 2018; 36(4):608-614IN

Abstract

Background Cisplatin and pemetrexed are very effective against advanced non-squamous non-small cell lung cancer (NSCLC) without EGFR mutations. Erlotinib plus bevacizumab are highly effective against advanced NSCLCs with activating EGFR mutations. We performed this phase I 'Quartet Trial' to determine the safety and efficacy of all 4 agents as a first-line treatment for non-squamous NSCLC patients harboring activating EGFR mutations. Patients and Methods Patients received escalating quartet-agent doses every 3 weeks for 4 cycles. We examined the dose-limiting toxicity (DLT) to determine the maximum tolerated dose (MTD) and recommended dose (RD). Results Ten patients (3 men and 7 women) with a median age of 69 years were enrolled. Four and 6 patients had exon 19 and 21 mutations, respectively; 8 received maintenance therapy without unexpected or cumulative toxicities. One of 6 patients experienced grade 3 vagal reflex at 60 mg/m2 cisplatin plus 500 mg/m2 pemetrexed with 150 mg erlotinib and 15 mg/kg bevacizumab, which was designated the RD. Four patients experienced no DLT with 75 mg/m2 cisplatin plus 500 mg/m2 pemetrexed with 150 mg erlotinib and 15 mg/kg bevacizumab (designated the MTD); however, 3 underwent dose reduction due to severe toxicities (grade 3 gastrointestinal hemorrhage, skin rash, nausea, and febrile neutropenia) during induction chemotherapy. The most frequent DLT-phase adverse events were nausea, anorexia, and fatigue. The overall response rate was 100%. Furthermore, the progression-free and overall survival rates were 17.9 and 32.0 months, respectively. Conclusions This quartet chemotherapy regimen was tolerable and effective in our patient population (UMIN000012536).

Authors+Show Affiliations

Department of Thoracic Oncology, Osaka International Cancer Institute, 3-1-69 Otemachi Chuo-ku, Osaka, 541-8567, Japan. moto19781205@yahoo.co.jp.Department of Internal Medicine, Kinki-chuo Chest Medical Center, Sakai, Japan.Department of Thoracic Malignancy, Osaka Prefectural Hospital Organization Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Japan.Department of Thoracic Malignancy, Osaka Prefectural Hospital Organization Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Japan.Department of Internal Medicine, Kinki-chuo Chest Medical Center, Sakai, Japan.Department of Internal Medicine, Kinki-chuo Chest Medical Center, Sakai, Japan.Department of Internal Medicine, Kinki-chuo Chest Medical Center, Sakai, Japan.Department of Thoracic Malignancy, Osaka Prefectural Hospital Organization Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Japan.Department of Thoracic Malignancy, Osaka Prefectural Hospital Organization Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Japan.Department of Thoracic Malignancy, Osaka Prefectural Hospital Organization Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Japan.Department of Clinical Research Center, Kinki-chuo Chest Medical Center, Sakai, Japan.Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.Department of Clinical Research Center, Kinki-chuo Chest Medical Center, Sakai, Japan.Department of Internal Medicine, Kinki-chuo Chest Medical Center, Sakai, Japan.

Pub Type(s)

Clinical Trial, Phase I
Journal Article

Language

eng

PubMed ID

29101518

Citation

Tamiya, Motohiro, et al. "Phase1 Study of Cisplatin Plus Pemetrexed With Erlotinib and Bevacizumab for Chemotherapy-naïve Advanced Non-squamous Non-small Cell Lung Cancer With EGFR Mutations." Investigational New Drugs, vol. 36, no. 4, 2018, pp. 608-614.
Tamiya M, Tamiya A, Shiroyama T, et al. Phase1 study of cisplatin plus pemetrexed with erlotinib and bevacizumab for chemotherapy-naïve advanced non-squamous non-small cell lung cancer with EGFR mutations. Invest New Drugs. 2018;36(4):608-614.
Tamiya, M., Tamiya, A., Shiroyama, T., Takeoka, S., Naito, Y., Omachi, N., ... Hirashima, T. (2018). Phase1 study of cisplatin plus pemetrexed with erlotinib and bevacizumab for chemotherapy-naïve advanced non-squamous non-small cell lung cancer with EGFR mutations. Investigational New Drugs, 36(4), pp. 608-614. doi:10.1007/s10637-017-0527-z.
Tamiya M, et al. Phase1 Study of Cisplatin Plus Pemetrexed With Erlotinib and Bevacizumab for Chemotherapy-naïve Advanced Non-squamous Non-small Cell Lung Cancer With EGFR Mutations. Invest New Drugs. 2018;36(4):608-614. PubMed PMID: 29101518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phase1 study of cisplatin plus pemetrexed with erlotinib and bevacizumab for chemotherapy-naïve advanced non-squamous non-small cell lung cancer with EGFR mutations. AU - Tamiya,Motohiro, AU - Tamiya,Akihiro, AU - Shiroyama,Takayuki, AU - Takeoka,Sawa, AU - Naito,Yujiro, AU - Omachi,Naoki, AU - Kimura,Yohei, AU - Morishita,Naoko, AU - Suzuki,Hidekazu, AU - Okamoto,Norio, AU - Okishio,Kyoichi, AU - Kawaguchi,Tomoya, AU - Atagi,Shinji, AU - Hirashima,Tomonori, Y1 - 2017/11/04/ PY - 2017/09/11/received PY - 2017/10/22/accepted PY - 2017/11/5/pubmed PY - 2019/3/28/medline PY - 2017/11/5/entrez KW - Combination chemotherapy KW - Epidermal growth factor receptor KW - Maintenance therapy KW - Non-small cell lung cancer SP - 608 EP - 614 JF - Investigational new drugs JO - Invest New Drugs VL - 36 IS - 4 N2 - Background Cisplatin and pemetrexed are very effective against advanced non-squamous non-small cell lung cancer (NSCLC) without EGFR mutations. Erlotinib plus bevacizumab are highly effective against advanced NSCLCs with activating EGFR mutations. We performed this phase I 'Quartet Trial' to determine the safety and efficacy of all 4 agents as a first-line treatment for non-squamous NSCLC patients harboring activating EGFR mutations. Patients and Methods Patients received escalating quartet-agent doses every 3 weeks for 4 cycles. We examined the dose-limiting toxicity (DLT) to determine the maximum tolerated dose (MTD) and recommended dose (RD). Results Ten patients (3 men and 7 women) with a median age of 69 years were enrolled. Four and 6 patients had exon 19 and 21 mutations, respectively; 8 received maintenance therapy without unexpected or cumulative toxicities. One of 6 patients experienced grade 3 vagal reflex at 60 mg/m2 cisplatin plus 500 mg/m2 pemetrexed with 150 mg erlotinib and 15 mg/kg bevacizumab, which was designated the RD. Four patients experienced no DLT with 75 mg/m2 cisplatin plus 500 mg/m2 pemetrexed with 150 mg erlotinib and 15 mg/kg bevacizumab (designated the MTD); however, 3 underwent dose reduction due to severe toxicities (grade 3 gastrointestinal hemorrhage, skin rash, nausea, and febrile neutropenia) during induction chemotherapy. The most frequent DLT-phase adverse events were nausea, anorexia, and fatigue. The overall response rate was 100%. Furthermore, the progression-free and overall survival rates were 17.9 and 32.0 months, respectively. Conclusions This quartet chemotherapy regimen was tolerable and effective in our patient population (UMIN000012536). SN - 1573-0646 UR - https://www.unboundmedicine.com/medline/citation/29101518/Phase1_study_of_cisplatin_plus_pemetrexed_with_erlotinib_and_bevacizumab_for_chemotherapy_naïve_advanced_non_squamous_non_small_cell_lung_cancer_with_EGFR_mutations_ L2 - https://doi.org/10.1007/s10637-017-0527-z DB - PRIME DP - Unbound Medicine ER -