Efficacy, Safety, and Cost-Minimization Analysis of Continuous Infusion of Low-Dose Gemcitabine Plus Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma

Our plain-English summary of Efficacy, Safety, and Cost-Minimization Analysis of Continuous Infusion of Low-Dose Gemcitabine Plus Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma, by O. Arrieta, W. Muñoz-Montaño, S. Muñiz-Hernández, et al (Frontiers in Oncology, 2021).

The study

• Authors: O. Arrieta, W. Muñoz-Montaño, S. Muñiz-Hernández, S. Campos, R. Catalán, H. Soto-Molina, S. Guzmán Vázquez, O. Díaz-Álvarez, V. Martínez-Pacheco, J.G. Turcott, M. Ramos-Ramírez, L. Cabrera-Miranda, F. Barrón, A.F. Cardona
• Journal: Frontiers in Oncology
• Published: 2021;11:641975
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is rare and aggressive neoplasia, with a poor prognosis; furthermore, the monetary cost of its treatment represents a major challenge for many patients. The economic burden this malignancy imposes is underscored by the fact that asbestos exposure, which is the most frequent risk factor, is much more prevalent in the lower socioeconomic population of developing countries. The aims of the present study were to evaluate the efficacy, safety, and cost of continuous infusion of low-dose Gemcitabine plus Cisplatin (CIGC) as a treatment strategy for patients with unresectable MPM.

Methods: We performed a prospective cohort study to determine efficacy and safety of continuous infusion gemcitabine at a dose of 250 mg/m2 in a 6-h continuous infusion plus cisplatin 35 mg/m2 on days 1 and 8 of a 21-day cycle in patients with unresectable MPM. We also performed a cost-minimization analysis to determine if this chemotherapy regimen is less expensive than other currently used regimens.

Results: The median number of chemotherapy cycles was six (range 1-11 cycles); objective response rate was documented in 46.2%, and disease control rate was seen in 81.2%. Median PFS was 8.05 months (CI 95% 6.97-9.13); median OS was 16.16 months (CI 95% 12.5-19.9). The cost minimization analysis revealed savings of 66.4, 61.9, and 97.7% comparing CIGC with short-infusion gemcitabine plus cisplatin (SIGC), cisplatin plus pemetrexed (CP), and cisplatin plus pemetrexed and bevacizumab (CPB), respectively. Furthermore, this chemotherapy regimen proved to be safe at the administered dosage.

Conclusion: CIGC is an effective and safe treatment option for patients with unresectable MPM; besides, this combination is a cost-saving option when compared with other frequently used chemotherapy schemes. Therefore, this treatment scheme should be strongly considered for patients with unresectable MPM and limited economic resources.

Copyright © 2021 Arrieta, Muñoz-Montaño, Muñiz-Hernández, Campos, Catalán, Soto-Molina, Guzmán Vázquez, Díaz-Álvarez, Martínez-Pacheco, Turcott, Ramos-Ramírez, Cabrera-Miranda, Barrón and Cardona.

In plain English

This Mexico City study followed 80 patients with unresectable stage III or IV malignant pleural mesothelioma treated from 2009 to 2019. They received low-dose gemcitabine by 6-hour continuous infusion plus cisplatin, or carboplatin if unsuitable for cisplatin (number not reported). Asbestos exposure was recorded in 37 of 80 (46.2%), possibly underestimated because of recall bias, the authors said. A partial or complete response occurred in 46.2% of patients and disease control in 81.2%. Median progression-free survival was 8.05 months (95% CI 6.97 to 9.13) and median overall survival 16.16 months (95% CI 12.5 to 19.9). Overall survival did not differ significantly by asbestos exposure. Severe neutropenia affected 12.5%. A cost analysis compared the regimen with three others not given in this study: short-infusion gemcitabine plus cisplatin, cisplatin plus pemetrexed, and cisplatin plus pemetrexed and bevacizumab, assuming all four were equally effective. For a public hospital in Mexico, estimated six-cycle savings were 66.4%, 61.9% and 97.7%, respectively. The authors concluded the regimen is effective, safe and cost-saving, but said their single-arm, single-center results should be confirmed in randomized 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-arm cohort study of one chemotherapy regimen, with a cost-minimization analysis. Costs of the comparison regimens were estimated rather than measured in study patients.
• Who was studied: 80 patients with unresectable stage III or IV malignant pleural mesothelioma, treated at the Instituto Nacional de Cancerología, Mexico City, from January 2009 to July 2019.
• Exposure: The exposure studied was the treatment: gemcitabine 250 mg/m2 as a 6-hour continuous infusion plus cisplatin 35 mg/m2 on days 1 and 8 of a 21-day cycle. Patients not suitable for cisplatin received carboplatin instead; the article does not say how many. Asbestos exposure was recorded only as a baseline patient characteristic.
• Main results:
  • Asbestos exposure was present in 46.2% of the 80 patients (37 patients, per Table 1).
  • Objective response (partial or complete) was seen in 46.2% of patients, and disease control in 81.2%.
  • For all 80 patients, median progression-free survival was 8.05 months (95% CI 6.97 to 9.13) and median overall survival was 16.16 months (95% CI 12.5 to 19.9).
  • Median overall survival was 15.54 months in the 43 patients without asbestos exposure and 17.74 months in the 37 with asbestos exposure (p = 0.330). This difference was not statistically significant.
  • No baseline factor was significantly associated with progression-free survival. Only gender and Karnofsky performance status were significantly associated with overall survival.
  • The most common side effects were fatigue (77.5%), nausea (75%), leukopenia (42%) and vomiting (33.8%). Severe (grade 3 to 4) neutropenia occurred in 10 patients (12.5%).
  • After two cycles, functional role, emotional role and pain improved to a clinically significant degree on the quality-of-life questionnaire, while nausea and vomiting got significantly worse.
  • In the public-hospital analysis, estimated mean total cost per patient was $367.57 for the study regimen, $1,092.75 for short-infusion gemcitabine plus cisplatin, $16,020.69 for cisplatin plus pemetrexed and bevacizumab, and $964.56 for cisplatin plus pemetrexed.
  • In the public-hospital analysis (six-cycle time horizon), the study regimen saved an estimated 66.4% compared with short-infusion gemcitabine plus cisplatin, 61.9% compared with cisplatin plus pemetrexed, and 97.7% compared with cisplatin plus pemetrexed and bevacizumab.
  • In the private-hospital analysis, estimated savings with the study regimen were 46.5% compared with short-infusion gemcitabine plus cisplatin, 89.4% compared with cisplatin plus pemetrexed and bevacizumab, and 54.3% compared with cisplatin plus pemetrexed.
• The authors' conclusion: The authors concluded that continuous infusion of low-dose gemcitabine plus cisplatin is an effective and safe option for unresectable malignant pleural mesothelioma. They also concluded it saves money compared with the three other regimens, but said their results should be confirmed by multicenter randomized trials.
• Limitations the authors state:
  • Single-arm design, with no direct comparison with other treatments.
  • The cost analysis assumed the study regimen was as effective as the three comparison regimens.
  • Social costs may be underestimated because caregiver costs were not included.
  • A relatively high number of patients were censored from the survival analysis, largely because of loss to follow-up.
  • Quality of life was assessed only after two chemotherapy cycles.
  • The proportion with asbestos exposure may be underestimated because of recall bias.
  • No cost comparison was made with the newly approved immunotherapy regimen (ipilimumab plus nivolumab).
  • Generic and biosimilar versions of pemetrexed and bevacizumab could change the cost comparisons.
  • Single-arm, single-center design; results need confirmation in multicenter randomized trials.

Topics

Medical terms in this study, explained in our Lexicon: Gemcitabine, Cisplatin, Unresectable, Pleural Mesothelioma, Prognosis, Asbestos Exposure, Cohort Study, Chemotherapy.

Related studies

• A phase II trial of prolonged, continuous infusion of low-dose gemcitabine plus cisplatin in patients with advanced malignant pleural mesothelioma — O. Arrieta, D. López-Macías, et al. (2014)
• Bevacizumab plus cisplatin/pemetrexed then bevacizumab alone for unresectable malignant pleural mesothelioma: A Japanese safety study — T. Nakano, K. Kuribayashi, et al. (2021)
• A phase II trial of low-dose gemcitabine in a prolonged infusion and cisplatin for malignant pleural mesothelioma — V. Kovac, M. Zwitter, et al. (2012)
• Cost-effectiveness analysis of additional bevacizumab to pemetrexed plus cisplatin for malignant pleural mesothelioma based on the MAPS trial — M. Zhan, H. Zheng, et al. (2017)
• Raltitrexed plus cisplatin is cost-effective compared with pemetrexed plus cisplatin in patients with malignant pleural mesothelioma — B. Woods, N. Paracha, et al. (2012)
• Comparison of cisplatin plus pemetrexed and cisplatin plus gemcitabine for the treatment of malignant pleural mesothelioma in Japanese patients — T. Shukuya, T. Takahashi, et al. (2014)

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