Combined treatment with pemetrexed and vinflunine in patients with metastatic urothelial cell carcinoma after prior platinum-containing chemotherapy - results of an exploratory phase I study
| Autor: | Anders Ullén, H. von der Maase, Mads Agerbæk, Helle Pappot |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Male Organoplatinum Compounds medicine.medical_treatment chemistry.chemical_compound 0302 clinical medicine Antineoplastic Combined Chemotherapy Protocols Pharmacology (medical) Vinflunine Urinary Bladder Neoplasms/drug therapy Middle Aged Combined Modality Therapy Europe Pemetrexed 030220 oncology & carcinogenesis Toxicity Female Urologic Neoplasms/drug therapy medicine.drug medicine.medical_specialty Urologic Neoplasms Anemia Vinblastine/administration & dosage Carcinoma Transitional Cell/drug therapy Neutropenia Vinblastine Disease-Free Survival 03 medical and health sciences Internal medicine medicine Humans Organoplatinum Compounds/administration & dosage Adverse effect Aged Pharmacology Chemotherapy Carcinoma Transitional Cell business.industry medicine.disease Surgery 030104 developmental biology chemistry Urinary Bladder Neoplasms Antineoplastic Combined Chemotherapy Protocols/therapeutic use business Pemetrexed/administration & dosage Progressive disease |
| Zdroj: | Pappot, H, von der Maase, H, Ullén, A, Agerbæk, M & NUCOG-Nordic Urothelial Cancer Oncology Group (NUCOG) 2018, ' Combined treatment with pemetrexed and vinflunine in patients with metastatic urothelial cell carcinoma after prior platinum-containing chemotherapy-results of an exploratory phase I study ', Investigational New Drugs, vol. 36, no. 4, pp. 615-618 . https://doi.org/10.1007/s10637-017-0528-y |
| ISSN: | 1573-0646 |
| Popis: | Vinflunine is to date the only registered agent for second-line treatment of metastatic urothelial cell carcinoma (UCC) in Europe. However, the effect is modest. Pemetrexed has demonstrated some single-agent activity in this disease entity. In order to improve treatment possibilities for UCC patients, a phase I trial (VINTREX) was undertaken to assess the safety of vinflunine and pemetrexed in metastatic UCC patients. A dose escalation design was planned to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of a vinflunine/pemetrexed combination. Pemetrexed was added to vinflunine dosed at 280 mg/m2 on day 1 of a 21-day cycle. Three levels of pemetrexed were planned starting at 400 mg/m2. Four patients were enrolled with a mean age of 66 years and with a mean number of prior GC-cycles of 6,8. Two DLT's were observed at the lowest dose-level in cohort 1. One patient experienced grade 4 thrombocytopenia and a second demonstrated hepatobiliary toxicity grade 3 with an increase in alanine aminotransaminase. Most common grade 3 and 4 adverse events were anemia, thrombocytopenia and neutropenia. Three out of four patients received 3 cycles of pemetrexed and vinflunine, all had progressive disease. Based on these observations and due to protocol design, the study was interrupted at dose level 1 for safety reasons. The combined therapy of vinflunine (Javlor®, Pierre Fabre Pharma) and pemetrexed (Alimta®, Eli Lilly) is poorly tolerated in metastatic UCC patients. The combination cannot be recommended for further investigations in metastatic UCC. Vinflunine is to date the only registered agent for second-line treatment of metastatic urothelial cell carcinoma (UCC) in Europe. However, the effect is modest. Pemetrexed has demonstrated some single-agent activity in this disease entity. In order to improve treatment possibilities for UCC patients, a phase I trial (VINTREX) was undertaken to assess the safety of vinflunine and pemetrexed in metastatic UCC patients. A dose escalation design was planned to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of a vinflunine/pemetrexed combination. Pemetrexed was added to vinflunine dosed at 280 mg/m2 on day 1 of a 21-day cycle. Three levels of pemetrexed were planned starting at 400 mg/m2. Four patients were enrolled with a mean age of 66 years and with a mean number of prior GC-cycles of 6,8. Two DLT's were observed at the lowest dose-level in cohort 1. One patient experienced grade 4 thrombocytopenia and a second demonstrated hepatobiliary toxicity grade 3 with an increase in alanine aminotransaminase. Most common grade 3 and 4 adverse events were anemia, thrombocytopenia and neutropenia. Three out of four patients received 3 cycles of pemetrexed and vinflunine, all had progressive disease. Based on these observations and due to protocol design, the study was interrupted at dose level 1 for safety reasons. The combined therapy of vinflunine (Javlor®, Pierre Fabre Pharma) and pemetrexed (Alimta®, Eli Lilly) is poorly tolerated in metastatic UCC patients. The combination cannot be recommended for further investigations in metastatic UCC. |
| Databáze: | OpenAIRE |
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