Cisplatin and irinotecan (CPT-11) for peritoneal mesothelioma

Our plain-English summary of Cisplatin and irinotecan (CPT-11) for peritoneal mesothelioma, by D.T. Le, M. Deavers, K. Hunt, et al (Cancer Investigation, 2003).

The study

• Authors: D.T. Le, M. Deavers, K. Hunt, A. Malpica, C.F. Verschraegen
• Journal: Cancer Investigation
• Published: 2003;21(5):682-9
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Peritoneal mesothelioma is a rare malignancy that is seen in patients exposed to asbestos or in young women with no known exposure to asbestos. The clinical features of the disease are similar in these two groups, and include peritoneal carcinomatosis, ascites, thrombocytemia, systemic symptoms (fever and night sweats), and hypercoagulability. There is no known curative therapy for this disease. Cisplatin has activity in 25% of patients. Mesothelial cells are known to contain high levels of carboxylesterase, a key enzyme in the activation of Irinotecan (CPT-11) to SN-38. This retrospective review of our experience in combining cisplatin 50 or 60 mg/m2 i.v. or i.p. on day 1 with CPT-11 50 or 60 mg/m2 i.v. on day 1, 8, and 15. Courses were repeated every 4 weeks x 6. If i.p. administration of cisplatin were feasible, it was the preferred route. Response to treatment was based on RECIST criteria. Fourteen men and 3 women, median age 62 years (35-76 years) and median PS 1 (0-2) were treated. Median number of courses was two for nonresponders and six for responders. The overall response rate was 24%, but 76% of patients improved on treatment. Median survival is not reached. Grade > or = 2 side effects included anemia (n = 6), neutropenia (n = 3), nausea/vomiting (n = 4), and constipation (n = 2). Grade 1 side effects were fatigue, anorexia, weight loss, alopecia, diarrhea, neuropathy, and gastric reflux. There were no grade > or = 3 hematologic toxicities. The combination of cisplatin and CPT-11 is well tolerated and has clinical benefits in patients with peritoneal mesothelioma.

In plain English

This retrospective review of records at The University of Texas M. D. Anderson Cancer Center covered 17 patients with peritoneal mesothelioma (14 men, 3 women, aged 35 to 76). They received cisplatin and irinotecan (CPT-11) between August 1999 and May 2001. Sixteen had primary peritoneal disease; in one, it began in the pleura. A history of asbestos exposure was recorded in 4 men and unknown in 5. Cisplatin was given into the abdomen when feasible, otherwise into a vein; irinotecan was given into a vein, for up to six 4-week cycles. Four patients (24%) had a partial response, 9 (52%) had stable disease and 4 (24%) had disease progression. Of 6 patients with ascites, 2 had complete resolution. Anemia and low granulocyte (white blood cell) counts were the main blood-related side effects, none at grade 3. The authors called nausea and vomiting the predominant side effect. One patient had grade 3 vomiting; none needed a dose reduction. When reported, 11 patients were alive and median survival had not been reached. The authors concluded the combination was very safe with modest activity.

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: Retrospective review of medical records of patients treated with a chemotherapy combination (single-center case series)
• Who was studied: 17 patients with peritoneal mesothelioma (14 men, 3 women; median age 62, range 35 to 76) treated at The University of Texas M. D. Anderson Cancer Center, Houston, between August 1999 and May 2001. Sixteen had primary peritoneal mesothelioma and 1 had onset of disease in the pleura.
• Exposure: The study examined a treatment, not an asbestos exposure. Patients received cisplatin 60 or 50 mg/m2 (intraperitoneal or intravenous) on day 1 plus intravenous irinotecan 60 or 50 mg/m2 on days 1, 8 and 15 of a 28-day cycle, for a maximum of 6 cycles. Asbestos exposure history was yes in 4 male patients, no in 8 and unknown in 5. Fiber types were not reported.
• Main results:
  • 4 of 17 patients (24%) had a partial response. No complete responses were observed.
  • Disease remained stable in 9 patients (52%), and 4 patients (24%) had progression after two courses.
  • Of 6 patients with ascites, 2 had complete resolution of the ascites, and in the other 4 the rate of reaccumulation slowed.
  • Granulocytopenia and anemia were the main hematologic (blood-related) toxicities. Anemia was grade 2 in 6 patients and grade 1 in 7. Granulocytopenia was grade 2 in 3 patients and grade 1 in 5. There was no thrombocytopenia.
  • The authors described nausea and emesis (vomiting) as the predominant side effect and said hematopoietic toxicity was not significant.
  • One patient had grade 3 vomiting (emesis), and no patient required a dose reduction.
  • At the time of reporting, 11 patients were alive and median survival had not been reached. Response duration for responders was 36 weeks (range 5+ to 47+ weeks).
• The authors' conclusion: The authors concluded that intravenous irinotecan combined with intraperitoneal or intravenous cisplatin is very safe and has modest activity in patients with peritoneal mesothelioma. They said a comparison with a gemcitabine- or pemetrexed-based combination is warranted.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Cisplatin, Peritoneal Mesothelioma, Ascites, Mesothelial Cells, Median Survival, Neutropenia.

Related studies

• Docetaxel and irinotecan (CPT-11) in the treatment of malignant pleural mesothelioma--a feasibility study — A. Knuuttila, T. Ollikainen, et al. (2000)
• Future directions for clinical research with CPT-11 (irinotecan) — D. von Hoff (1996)
• Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for malignant peritoneal mesothelioma: mitomycin versus cisplatin — A.U. Blackham, P. Shen, et al. (2010)
• The maximum tolerated dose and biologic effects of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) in combination with irinotecan for patients with refractory solid tumors — B.S. Choi, D.B. Alberti, et al. (2010)
• Systemic chemotherapy with pemetrexed and cisplatin for malignant peritoneal mesothelioma: a single institution experience — G. Lainakis, F. Zagouri, et al. (2011)
• Complete pathological response to neoadjuvant pemetrexed/cisplatin in combination with regional hyperthermia in a patient with sarcomatoid peritoneal mesothelioma — S. Kruger, M.K. Angele, et al. (2014)

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