Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma

Our plain-English summary of Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma, by J.B. Sørensen, H. Frank, T. Palshof (British Journal of Cancer, 2008).

The study

• Authors: J.B. Sørensen, H. Frank, T. Palshof
• Journal: British Journal of Cancer
• Published: 2008;99(1):44-50
• Cited by: 46 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The aim was to evaluate the activity of cisplatin and vinorelbine in previously untreated, inoperable patients having histologically verified malignant pleural mesothelioma (MPM), normal organ function, and performance status 0-2. Treatment was vinorelbine 25 mg m(-2) i.v. weekly and cisplatin 100 mg m(-2) i.v. every 4 weeks with hydration and standard prophylactic antiemetic treatment. Patients gave written informed consent. Characteristics of 54 consecutive patients were: males 85%, epithelial subtype 74%, IMIG stages III and IV 35 and 46%, performance status 0, 1, and 2, 26, 69, and 6%, and median age 63 years (31-78 years). CTC grade 3 or 4 toxicity occurred with respect to leukocytopenia (48% of patients, grade 4 in 13%), nausea (13%), neurotoxicity (11%), nephrotoxicity (4%), and other toxicities (9%). There were no toxic deaths. The median number of cycles was four. The fraction of patients alive at 1-, 2-, and 3-years were 61, 31, and 4%, respectively, and median survival and median time to progression were 16.8 months (0.5 to 46.4 +months) and 7.2 months (1.6 to 40.6 + months). There were two CRs and 14 PRs (response rate 29.6%). Cisplatin and intravenous vinorelbine is a highly active regimen in MPM with a response rate and survival comparable to the most active regimens so far reported.

In plain English

This study treated 54 consecutive patients with malignant pleural mesothelioma that could not be operated on and who had not had chemotherapy before. They were enrolled between February 2003 and September 2006 and given cisplatin every 4 weeks plus vinorelbine weekly. There was no comparison group, and the authors stated it was not a formal phase II trial. Previous asbestos exposure was recorded in 76% of patients. Tumours responded in 16 patients (2 complete and 14 partial responses), an overall response rate of 29.6% (95% confidence limits 18.0 to 43.6%). Median overall survival was 16.8 months and median time to disease progression was 7.2 months. 61% were alive after 1 year and 31% after 2 years. Grade 3 or 4 (severe) low white blood cell counts occurred in 48% of patients, and 17% were hospitalised for side effects. The authors concluded the combination ranked among the most active chemotherapy treatments reported for this disease. They called it inconvenient because of the weekly infusions and blood toxicity, and cautioned that the results come from relatively small, non-randomised trials.

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: Prospective single-group treatment study (not a formal phase II trial), with no comparison group
• Who was studied: 54 consecutive patients with histologically proven, inoperable malignant pleural mesothelioma and no previous chemotherapy, enrolled February 2003 to September 2006. 85% were male, 74% had the epithelial subtype, 81% were IMIG stage III to IV, and the median age was 63 years (range 31 to 78). The authors are from three Danish oncology departments.
• Exposure: The study examined a treatment, not an asbestos exposure: cisplatin 100 mg per square metre of body surface by 1-hour intravenous infusion every 4 weeks, plus vinorelbine 25 mg per square metre intravenously every week. Previous asbestos exposure was recorded as a patient characteristic (76%) but was not analysed.
• Main results:
  • Of the 54 patients, 2 had a complete response (3.7%) and 14 a partial response (25.9%), for an overall response rate of 29.6% (95% confidence limits 18.0 to 43.6%).
  • Median time to progression was 7.2 months and median overall survival was 16.8 months.
  • 61% of patients were alive after 1 year and 31% after 2 years.
  • Responses by tumour type: 13 of the 40 patients with epithelial subtype responded (32.5%). By sex, 4 of 8 women (50%) and 12 of 46 men (26%) responded; the article prints P = 0.45 for this comparison.
  • Grade 3 or 4 leukopenia (low white blood cell count) occurred in 26 patients (48%), including grade 4 in 6 patients (11%).
  • Five patients (9%) had febrile leukopenia; there were no septic deaths.
  • Nine patients (17%) were hospitalised because of toxic effects of chemotherapy, and dose reductions were needed in 19 patients (35%).
  • One patient died within 30 days of starting treatment, owing to a pulmonary embolism.
  • 22 patients (41%) received second-line chemotherapy after the study treatment.
• The authors' conclusion: The authors concluded that cisplatin plus vinorelbine ranks among the most active cytotoxic treatments reported for malignant pleural mesothelioma. They also judged the regimen inconvenient for patients and the health-care system because of the weekly intravenous vinorelbine and the blood toxicity.
• Limitations the authors state:
  • The authors stated the results come from relatively small, non-randomised trials with wide confidence limits.
  • Comparisons with other regimens are affected by differences in patients' prognostic factors between trials.
  • The proportion of patients with epithelial subtype (74%) was higher than the roughly 60% usual in the overall mesothelioma population, which may have contributed to a higher response rate.
  • Second-line chemotherapy in 22 patients may have affected survival, but the authors stated this could not be explored from these data.
  • Different response-measurement systems used across reports may contribute to variation in response rates.

Topics

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

Medical terms in this study, explained in our Lexicon: Cisplatin, Vinorelbine, Chemotherapy, Pleural Mesothelioma, Performance Status, Informed Consent, IMIG, Nephrotoxicity.

Related studies

• Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy — G. Toyokawa, M. Takenoyama, et al. (2014)
• Triplet chemotherapy with cisplatin, gemcitabine and vinorelbine for malignant pleural mesothelioma — R. Maruyama, F. Shoji, et al. (2005)
• JME-001 phase II trial of first-line combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable malignant pleural mesothelioma — Y. Miyamoto, T. Kozuki, et al. (2021)
• Chemotherapy for malignant mesothelioma: from doxorubicin to vinorelbine — P. Baas (2002)
• Low ERCC1 expression in malignant pleural mesotheliomas treated with cisplatin and vinorelbine predicts prolonged progression-free survival — Z.G. Zimling, J.B. Sørensen, et al. (2012)
• A biomarker profile for predicting efficacy of cisplatin-vinorelbine therapy in malignant pleural mesothelioma — Z.G. Zimling, J.B. Sørensen, et al. (2012)

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