Phase I/II study of intraperitoneal mitoxantrone in refractory ovarian cancer

Our plain-English summary of Phase I/II study of intraperitoneal mitoxantrone in refractory ovarian cancer, by A.M. Oza, W. ten Bokkel Huinink, R. Dubbelman, et al (Annals of Oncology, 1994).

The study

• Authors: A.M. Oza, W. ten Bokkel Huinink, R. Dubbelman, O. Soepenberg, I. Mandjes, E. Aartsen, J.G. McVie
• Journal: Annals of Oncology
• Published: 1994;5(4):343-7
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Mitoxantrone has demonstrable clinical activity when administered intravenously in a wide range of malignancies. The feasibility and toxicity of intra-peritoneal administration was established in a phase I study. The optimal dose from the phase I was subsequently evaluated in a phase II study.

Patients And Methods: 19 patients with refractory malignancies and extensive abdominal disease (13 ovarian cancer, 4 breast cancer, 2 mesothelioma) were entered in a phase I study. The dose of intraperitoneal mitoxantrone was escalated from 10 mg/m2, administered in 21 of fluid via a Tenckhoff catheter, to 55 mg/m2, in increments of 5 mg/m2. Cycles were repeated every three weeks. Sixty-seven cycles of mitoxantrone were administered, the maximum tolerable dose being 25 mg/m2. A phase II study at this dose was conducted in 14 patients with refractory ovarian cancer, all of whom had previously received systemic platinum based therapy. Five of the 14 had also previously been treated with intraperitoneal carboplatin. Fifty-one cycles were administered.

Results: The dose limiting toxicity in the phase I study was peritoneal irritation and pain. Leucopenia was frequent at doses equal or greater than 30 mg/m2. Three complete remissions were documented in the phase I study (2 breast cancer and 1 ovarian cancer). There was no significant haematological toxicity in the phase II assessment, though local toxicity precluded further therapy in 2 patients. No objective responses were seen in the phase II evaluation.

Conclusions: These studies demonstrate the feasibility of intra-peritoneal mitoxantrone therapy in patients with peritoneal disease, but do not support its routine use in ovarian cancer.

In plain English

This was a two-part drug trial of mitoxantrone, a chemotherapy drug, given directly into the abdominal cavity through a catheter and left for 4 hours. The article does not discuss asbestos. The first part (phase I) enrolled 19 patients with advanced cancer confined to the abdomen: 13 with epithelial ovarian cancer, 4 with breast cancer and 2 with intraperitoneal mesothelioma. Doses were raised step by step from 10 to 55 mg/m2 over 67 cycles. The highest dose patients could tolerate was 25 mg/m2. At 30 mg/m2 or above, 23 of 28 cycles were associated with chemical peritonitis (grade 2 or above), compared with 12 of 39 cycles at lower doses. Three patients had complete remission: two with breast cancer and one with ovarian cancer. The second part (phase II) gave 25 mg/m2 to 14 patients with recurrent and refractory ovarian cancer who had previously received platinum-based treatment. No responses were seen. The authors concluded that the treatment was feasible but did not support its routine use in ovarian cancer.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Phase I dose-escalation study followed by a phase II study (clinical drug trial)
• Who was studied: Phase I: 19 patients with advanced malignancy confined to the peritoneal cavity (13 epithelial ovarian cancer, 4 breast cancer, 2 intraperitoneal mesothelioma; the mesothelioma patients had no prior therapy). Phase II: 14 patients with recurrent and refractory ovarian cancer, lesions less than 1 cm, all previously treated with platinum-based therapy. Treated at the Netherlands Cancer Institute, Amsterdam.
• Exposure: Intraperitoneal mitoxantrone (chemotherapy), 10 to 55 mg/m2 in phase I and 25 mg/m2 in phase II, given in dialysis fluid through a Tenckhoff catheter with a 4 hour dwell time, every 3 weeks. Asbestos exposure is not discussed.
• Main results:
  • Phase I: the maximally tolerated dose was 25 mg/m2 with a 4 hour dwell time.
  • Phase I: at doses of 30 mg/m2 or above, 23 of 28 cycles were associated with chemical peritonitis WHO grade 2 or above, compared with 12/39 cycles at lower doses.
  • Phase I: leucopenia (low white cell count) was increasingly common at higher doses.
  • Phase I: seven patients stopped before completing 6 cycles because of excessive toxicity.
  • Phase I: two breast cancer patients and one ovarian cancer patient achieved complete remission, at doses of 25, 50 and 20 mg/m2 respectively.
  • Phase II (14 ovarian cancer patients): no responses were documented, and progressive disease or treatment failure occurred in 11 patients.
  • Phase II: chemical peritonitis and pain caused early discontinuation in 2 patients. Haematological toxicity was not significant.
• The authors' conclusion: The authors concluded that intraperitoneal mitoxantrone was feasible in patients with extensive peritoneal disease but that the studies did not support its routine use in ovarian cancer.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Ovarian cancer.

Medical terms in this study, explained in our Lexicon: Ovarian Cancer, Mesothelioma, Carboplatin.

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