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Phase I/II study of adding intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis.

ABSTRACT: BACKGROUND:Intraperitoneal chemotherapy using paclitaxel is considered an experimental approach for treating peritoneal carcinomatosis. This study aimed to determine the recommended dose, and to evaluate the clinical efficacy and safety, of the combination of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis. METHODS:The frequencies of dose-limiting toxicities were evaluated, and the recommended dose was determined in phase I. The primary endpoint of the phase II analysis was overall survival rate at 1?year. Secondary endpoints were antitumour effects, symptom-relieving effects, safety and overall survival. RESULTS:The recommended doses of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel were 800, 75 and 20?mg/m2 respectively. Among 46 patients enrolled in phase II, the median time to treatment failure was 6·0 (range 0-22·6) months. The response and disease control rates were 21 of 43 and 41 of 43 respectively. Ascites disappeared in 12 of 30 patients, and cytology became negative in 18 of 46. The median survival time was 14·5?months, and the 1-year overall survival rate was 61 per cent. Conversion surgery was performed in eight of 46 patients, and those who underwent resection survived significantly longer than those who were not treated surgically (median survival not reached versus 12·4?months). Grade 3-4 haematological toxicities developed in 35 of 46 patients, whereas non-haematological adverse events occurred in seven patients. CONCLUSION:Adding intraperitoneal paclitaxel had clinical efficacy with acceptable tolerability.

SUBMITTER: Yamada S

PROVIDER: S-EPMC7689756 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Phase I/II study of adding intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis.

Yamada S S Fujii T T Yamamoto T T Takami H H Yoshioka I I Yamaki S S Sonohara F F Shibuya K K Motoi F F Hirano S S Murakami Y Y Inoue H H Hayashi M M Murotani K K Kitayama J J Ishikawa H H Kodera Y Y Sekimoto M M Satoi S S

The British journal of surgery 20200707 13

<h4>Background</h4>Intraperitoneal chemotherapy using paclitaxel is considered an experimental approach for treating peritoneal carcinomatosis. This study aimed to determine the recommended dose, and to evaluate the clinical efficacy and safety, of the combination of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis.<h4>Methods</h4>The frequencies of dose-limiting toxicities were evaluated, and the reco ...[more]

PMID: 32638367

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Project description:IntroductionMalignant peritoneal mesothelioma (MPM) is a rare, aggressive tumour arising primarily from the peritoneum. The only potentially curative treatment is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the majority of patients are not eligible to undergo this treatment. The benefit of systemic treatment for these patients is limited at the cost of considerable morbidity. Hence, there is a need for appropriate palliative treatment options for patients with MPM. As MPM rarely disseminates outside the abdominal cavity, these patients might benefit from local treatment. A higher, more effective dose of chemotherapy can directly be delivered at the site of the disease. Systemic uptake will be limited, likely resulting in less toxicity. The aim of the INTERACT MESO trial is to determine the maximum tolerable dose of intraperitoneal paclitaxel monotherapy in patients with MPM. Secondary endpoints are to assess safety and toxicity, feasibility and the pharmacokinetic profile of this treatment.Methods and analysisThe INTERACT MESO trial is a prospective, open-label, single-centre, phase I study with a classic three-plus-three dose escalation design. The study population consists of adult patients with primary MPM, without extra-abdominal disease, who are not eligible to undergo CRS-HIPEC. According to standard of care work-up for CRS-HIPEC, patients will undergo diagnostic laparoscopy to determine the feasibility of CRS-HIPEC. In case CRS-HIPEC is not considered feasible, a peritoneal port-a-cath (PAC) system will be placed. Through this PAC, 8-16 weekly cycles of intraperitoneal chemotherapy will be administered.Ethics and disseminationThe Central Committee on Research Involving Human Subjects (CCMO, The Hague, The Netherlands) and the Medical Research Ethics Committee (METC, Rotterdam, The Netherlands) have granted permission to carry out this study protocol. The results of this trial will be submitted for publication in a peer-reviewed scientific journal.Trial registration numberNL9718. EudraCT: 2021-003637-11.

Project description:BACKGROUND:Combination chemotherapy regimens including fluoropyrimidines as well as albumin-bound paclitaxel have shown promising results in patients with metastatic pancreatic adenocarcinoma (mPC). Based on the recently described excellent therapeutic index of capecitabine plus nab-paclitaxel in metastatic breast cancer, the present phase II trial was initiated. METHODS:Patients with previously untreated mPC were treated with capecitabine (825 mg/m(2) orally bid on days 1-15) and nab-paclitaxel (125 mg/m(2) intravenously on days 1 and 8) every 3 weeks. In patients without clinically relevant adverse reactions after the 1st treatment course (? grade 2 toxicities according to NCI-CTC vs. 4.0, exuding alopecia and fatigue of any degree) and adequate bone marrow function, the nab-paclitaxel dose was escalated to 100 mg/m(2) on days 1, 8 and 15 of each cycle; this intra-individual dose escalation was maintained during subsequent treatment courses if tolerated. The primary endpoint was objective response rate (ORR) according to RECIST criteria, assessed by an independent radiological review committee with evaluation performed every 2 months. RESULTS:Between 12/2013 and 01/2015, 30 patients were entered in this monocentric academic phase II trial. All patients had an ECOG performance status of 0-1, 80% had liver metastases and 23% had biliary stents in place at time of study initiation. Median CA19-9 was 1,004 U/mL (0.9-100.000 U/mL). In all patients except 2, a dose escalation of nab-paclitaxel after the 1st treatment course could be accomplished. The most common grade 3 adverse events (AEs) included transient sensory neuropathy (23%), (afebrile) neutropenia (17%), hand-foot-syndrome (13%) and phototoxic skin reaction (10%). Among 29 RECIST-response assessable patients, the ORR was 41.4% and stable disease (SD) was noted in 34.5%, resulting in a disease control rate (DCR) of 76%. After a median follow-up duration of 10.3 months (range, 1.9-19.0 months), 13/30 patients (43.3%) are presently being alive. CONCLUSIONS:The combination of capecitabine + nab-paclitaxel at these doses and scheduling was well tolerated and showed substantial antitumor efficacy.

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Phase I/II study of adding intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis.

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Phase I/II study of adding intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis.

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