Phase I/II trial of sequential treatment of nab-paclitaxel in combination with gemcitabine followed by modified FOLFOX chemotherapy in patients with untreated metastatic exocrine pancreatic cancer: Phase I results
| Autor: | Enrique Aranda, Manuel Benavides, Gema Durán Ogalla, Alfredo Carrato, Inma R. de Mena, Mercedes Rodríguez-Garrote, Jose María Vieitez, Laura García Bermejo, Carmen Guillén-Ponce, Alfredo Castillo, Susana Rodríguez, Inmaculada Ruiz de Mena |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Male Cancer Research medicine.medical_specialty Maximum Tolerated Dose Organoplatinum Compounds Paclitaxel medicine.medical_treatment Leucovorin Neutropenia Adenocarcinoma Gastroenterology Deoxycytidine Drug Administration Schedule 03 medical and health sciences 0302 clinical medicine FOLFOX Internal medicine Albumins Antineoplastic Combined Chemotherapy Protocols medicine Humans Aged Chemotherapy Performance status business.industry Middle Aged medicine.disease Gemcitabine Oxaliplatin Pancreatic Neoplasms Regimen 030104 developmental biology Oncology Tolerability 030220 oncology & carcinogenesis Female Fluorouracil business medicine.drug |
| Zdroj: | European journal of cancer (Oxford, England : 1990). 139 |
| ISSN: | 1879-0852 |
| Popis: | Background Although occasioned through different mechanisms, the potential neurotoxicity and also haematological toxicity of nab-paclitaxel and oxaliplatin-based chemotherapy regimen were studied in this trial, which aimed to determine the maximum-tolerated dose (MTD) and to evaluate safety and efficacy of the combination in a sequential regimen of nab-paclitaxel, gemcitabine (GEM) and modified FOLFOX (mFOLFOX) in untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Materials and methods Treatment consisted of nab-paclitaxel (125/100 mg/m2) plus GEM (1000/800 mg/m2) on days 1, 8 and 15, followed by mFOLFOX (oxaliplatin [85/75/65 mg/m2], 5-FU bolus [400/300/200 mg/m2], 5-FU infusion [2400/2000/1600 mg/m2]) on day 28, of a 42-day cycle. Patients were enrolled at the highest dose level with a subsequent 3 + 3 dose de-escalation plan. Results Eleven patients (median age = 61, 64% with performance status [PS] = 1) were eligible. All patients received the highest dose level. No de-escalation was needed. A dose-limiting toxicity was reported, an upper gastrointestinal haemorrhage. The MTD was nab-paclitaxel 125 mg/m2, GEM 1000 mg/m2, oxaliplatin 85 mg/m2, 5-FU bolus 400 mg/m2 and 5-FU infusion 2400 mg/m2. Common all-grade toxicities were neutropenia (73%), anaemia (55%), thrombocytopenia (55%) and asthenia (55%). Other relevant toxicities were paraesthesia (46%), nausea (36%), dysesthesia (27%) and pyrexia (27%). Objective response rate was 50% and disease control rate was 80%. Conclusions The regimen of nab-paclitaxel plus GEM followed by mFOLFOX showed favourable safety and tolerability profiles with significant anti-tumor activity. More data are being achieved in a randomised phase II trial, to confirm efficacy rates and dismiss long-term neurotoxicity concerns regarding the sequencing of nab-paclitaxel and oxaliplatin. |
| Databáze: | OpenAIRE |
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