Docetaxel and irinotecan (CPT-11) in the treatment of malignant pleural mesothelioma--a feasibility study

Our plain-English summary of Docetaxel and irinotecan (CPT-11) in the treatment of malignant pleural mesothelioma--a feasibility study, by A. Knuuttila, T. Ollikainen, M. Halme, et al (Anti-cancer Drugs, 2000).

The study

• Authors: A. Knuuttila, T. Ollikainen, M. Halme, P. Mali, L. Kivisaari, K. Linnainmaa, A. Jekunen, K. Mattson
• Journal: Anti-cancer Drugs
• Published: 2000;11(4):257-61
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We chose to treat malignant pleural mesothelioma with a combination of docetaxel and irinotecan (CPT-11), because there have been preliminary reports that CPT-11 is active against mesothelioma, and docetaxel and CPT-11 were the most active agents in our in vitro experiments in human mesothelioma cell lines. Fifteen previously untreated patients with pleural mesothelioma (IMIG Stage III-IV) were given docetaxel 60 mg/m2 followed by CPT-11 190 mg/m2 on day 1, repeated every 3 weeks. All the patients were evaluable for toxicity and 13 patients were evaluated for response. No objective responses (complete or partial) were achieved, but there were two minor responses (overall response rate 15%) each of a duration of 4 months. Three patients had stable disease (23%); median time to progression was 7 months. Median survival in all the patients was 8.5 months from the first chemotherapy cycle and 11 months from diagnosis. Toxicity was severe with seven of 15 patients suffering neutropenic fever and six of 15 patients grade 3-4 diarrhea. The trial was discontinued because of toxicity and lack of activity. We do not recommend the combination of docetaxel and CPT-11 using the schedule presented here for further investigation in malignant mesothelioma. However, CPT-11 and docetaxel, individually, still warrant further study in this disease, especially in combination with cisplatin.

In plain English

This was a small feasibility study from Finland testing a chemotherapy combination, docetaxel followed by irinotecan (CPT-11), in malignant pleural mesothelioma. Fifteen previously untreated patients with stage III or IV disease were enrolled between November 1997 and May 1999. Thirteen of them were known to have had occupational asbestos exposure. Each cycle gave docetaxel 60 mg/m2 then CPT-11 190 mg/m2 on day 1 of a 21-day cycle. Of 13 patients who could be assessed for response, none had a complete or partial response. Two had minor responses lasting 4 months (response rate 15%, 95% confidence interval 2 to 45%). Median survival was 8.5 months from the start of treatment and 11 months from diagnosis, and the 1-year survival rate was 47%. Side effects were severe: seven of 15 patients had neutropenic fever, six of 15 had grade 3 to 4 diarrhea, and three stopped after one cycle because of toxicity. The authors stopped the trial and did not recommend this combination, at this dose and schedule, for further study. They noted the small number of patients and the very advanced disease.

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: Single-group feasibility study of a chemotherapy combination (toxicity and activity), with a planned stop if fewer than two objective responses or unacceptable toxicity occurred
• Who was studied: 15 previously untreated patients with histologically confirmed malignant pleural mesothelioma, entered between November 1997 and May 1999 (Helsinki and Turku, Finland). 13 were male and 2 female, mean age 61. IMIG stage III in 3 and stage IV in 12. 13 (87%) were known to have had occupational asbestos exposure.
• Exposure: Treatment with docetaxel 60 mg/m2 by 1-hour infusion followed by CPT-11 (irinotecan) 190 mg/m2 by 1-hour infusion on day 1 of a 21-day cycle. Three cycles were planned, up to a maximum of six.
• Main results:
  • Among 13 patients evaluable for response, there were no complete or partial responses. Two patients had minor responses, giving an overall response rate of 15% (two of 13; 95% confidence interval 2 to 45%), each lasting 4 months.
  • Three patients had no change in disease status after three cycles. Their time to progression ranged from 4.5 to 8 months.
  • Among all 15 patients, median survival was 8.5 months from the start of treatment and 11 months from diagnosis. The 1-year survival rate was 47%.
  • Toxicity was severe. Seven of 15 patients (47%) had neutropenic fever, and six of 15 had grade 3 to 4 diarrhea. Three patients stopped treatment after the first cycle because of toxicity.
  • The amount of pleural effusion did not correlate with the toxicity observed.
• The authors' conclusion: The authors considered it unethical to continue the study because of the toxicity and poor results. They did not recommend docetaxel plus irinotecan at this dose and schedule for further study in mesothelioma. They stated that CPT-11 and docetaxel individually still warranted investigation, especially combined with platinum compounds.
• Limitations the authors state:
  • Only a small number of patients were enrolled.
  • All patients had very advanced disease, which affected survival.
  • Without measuring drug concentrations in body fluids, no conclusions could be drawn on the role of pleural fluid in CPT-11 toxicity.
  • Response rate may not be the best indicator of clinical benefit from chemotherapy.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, IMIG, Median Overall Survival, Chemotherapy, Cisplatin.

Related studies

• Malignant pleural mesothelioma: a phase II trial with docetaxel — D.A. Vorobiof, B.L. Rapoport, et al. (2002)
• In vitro sensitivity of normal human mesothelial and malignant mesothelioma cell lines to four new chemotherapeutic agents — T. Ollikainen, A. Knuuttila, et al. (2000)
• Phase II study of gemcitabine plus docetaxel as second-line treatment in malignant pleural mesothelioma: a single institution study — I. Tourkantonis, N. Makrilia, et al. (2011)
• Cisplatin and irinotecan (CPT-11) for peritoneal mesothelioma — D.T. Le, M. Deavers, et al. (2003)
• miR-34a expression, cell cycle arrest and cell death of malignant mesothelioma cells upon treatment with radiation, docetaxel or combination treatment — T. Ghawanmeh, U. Thunberg, et al. (2011)
• Future directions for clinical research with CPT-11 (irinotecan) — D. von Hoff (1996)

Browse more research in Anti-cancer Drugs, or return to medical research.