Prevalence of in vitro chemotherapeutic drug resistance in primary malignant pleural mesothelioma: result in a cohort of 203 resection specimens

Our plain-English summary of Prevalence of in vitro chemotherapeutic drug resistance in primary malignant pleural mesothelioma: result in a cohort of 203 resection specimens, by A.A. Mujoomdar, T.R. Tilleman, W.G. Richards, et al (The Journal of Thoracic and Cardiovascular Surgery, 2010).

The study

• Authors: A.A. Mujoomdar, T.R. Tilleman, W.G. Richards, R. Bueno, D.J. Sugarbaker
• Journal: The Journal of Thoracic and Cardiovascular Surgery
• Published: 2010;140(2):352-5
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: Optimizing the multimodality treatment of malignant pleural mesothelioma depends on many factors including an adequate chemotherapeutic response. Currently, chemotherapy regimens for patients with mesothelioma are empirically selected. In vitro chemotherapy resistance in human mesothelioma has not been reported. Our goal was to determine the prevalence of drug resistance in a large sample of malignant pleural mesothelioma using a commercially available assay.

Methods: Tumors specimens (n = 203) were cultured for analysis of chemoresistance using the extreme drug resistance assay. Evaluable results were obtained in 168 (168/203 = 83%) specimens. Each specimen was tested with 3 drugs: cisplatin, gemcitabine, and vinorelbine. Drug resistance was characterized as low, intermediate, or extreme. Median age was 64 years (30-85 years). Forty-four (26%) patients received neoadjuvant chemotherapy before sampling and testing. The distribution of histopathologic cell types was epithelial (103; 61%), mixed (57; 34%), and sarcomatoid (8; 5%).

Results: A significant proportion of tumors had extreme/intermediate drug resistance to cisplatin (27%), gemcitabine (31%), or vinorelbine (59%). Nineteen tumors (11%) had extreme/intermediate resistance to all 3 drugs. Resistance (extreme/intermediate) to cisplatin was more prevalent in epithelial tumors than in nonepithelial (33% vs 18%; P = .0394). No significant differences in chemoresistance were found in tumors of patients who had received neoadjuvant chemotherapy compared with those who had not.

Conclusions: The feasibility of performing off-site in vitro drug resistance assays on resected malignant mesothelioma specimens is reported. A significant proportion of mesothelioma tumors exhibited extreme/intermediate resistance to cisplatin, gemcitabine, or vinorelbine.

In plain English

This laboratory study, from Brigham and Women's Hospital in Boston, tested how tumor tissue from people with malignant pleural mesothelioma responded to three chemotherapy drugs: cisplatin, gemcitabine and vinorelbine. Fresh tumor samples from 203 surgical patients were tested by a commercial laboratory between 2006 and 2008. The cells grew well enough to give results in 168 (83%). Each sample was graded as having low, intermediate or extreme resistance to each drug. Intermediate or extreme resistance was found in 27% of tumors for cisplatin, 31% for gemcitabine and 59% for vinorelbine. Nineteen tumors (11%) showed this level of resistance to all three drugs. Cisplatin resistance was more common in epithelial tumors (33%) than in nonepithelial tumors (18%), a statistically significant difference. Resistance did not differ significantly between the 44 patients who had chemotherapy before sampling and those who had not. The authors concluded that this testing was feasible and that "a significant proportion" of tumors resisted these drugs. They noted that the test used single drugs only and could not test pemetrexed. The study did not examine asbestos exposure.

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-center laboratory (in vitro) drug-resistance study of tumor specimens, with clinical data gathered retrospectively from a patient registry
• Who was studied: 203 primary malignant pleural mesothelioma tumor samples from patients undergoing surgery at Brigham and Women's Hospital, Boston, assayed 2006 to 2008. 168 gave usable results. Of the 168, 139 were male and 29 female; median age was 64 years (range 30 to 85). Cell types were 103 epithelial, 57 mixed and 8 sarcomatoid.
• Exposure: No asbestos exposure was studied. Tumor cells were exposed in the laboratory to single chemotherapy drugs (cisplatin, gemcitabine or vinorelbine) using a commercial extreme drug resistance (EDR) assay.
• Main results:
  • Among evaluable tumors, intermediate or extreme resistance was found in 27% for cisplatin, 31% for gemcitabine and 59% for vinorelbine.
  • Nineteen tumors (11%) had intermediate or extreme resistance to all three drugs. Of the 17 tumors with extreme resistance to cisplatin, 15 (88%) also had extreme resistance to gemcitabine (n = 10) or vinorelbine (n = 9), and 4 (24%) had extreme resistance to all three.
  • Intermediate or extreme resistance to cisplatin was more common in epithelial tumors (33%) than nonepithelial tumors (18%), P = .0394. Differences in the same direction for gemcitabine (35% vs 25%, P = .1581) and vinorelbine (62% vs 54%, P = .2875) were described by the authors as trends.
  • Among the 44 of 168 patients who had chemotherapy before their specimens were tested, resistance did not differ significantly from those who had not. For extreme cisplatin resistance the odds ratio was 1.6, P = .2453. No significant differences were found between patients who were ultimately resectable and those who were not.
• The authors' conclusion: The authors concluded that shipping mesothelioma specimens for off-site resistance testing was feasible, and that a significant proportion of tumors had intermediate or extreme resistance to the three drugs. They said the effectiveness of assay-directed therapy needs to be tested in prospective trials.
• Limitations the authors state:
  • The assay tested single drugs only, while platinum-based combination treatment is standard for this disease.
  • Pemetrexed, a commonly used drug, could not be tested because it interferes with the assay's measurement method.

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, Chemotherapy, Mesothelioma, Cisplatin, Gemcitabine, Vinorelbine, Neoadjuvant Therapy, Sarcomatoid.

Related studies

• Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma — M.G. Zauderer, S.L. Kass, et al. (2014)
• Interferon-alpha and -gamma in combination with chemotherapeutic drugs: in vitro sensitivity studies in four human mesothelioma cell lines — A.M. Hand, K. Husgafvel-Pursiainen, et al. (1992)
• 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)
• In vitro screening of synergistic ascorbate-drug combinations for the treatment of malignant mesothelioma — S. Martinotti, E. Ranzato, et al. (2011)
• Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection — D.J. Sugarbaker, R.R. Gill, et al. (2013)
• Interaction and cross-resistance of cisplatin and pemetrexed in malignant pleural mesothelioma cell lines — M. Kitazono-Saitoh, Y. Takiguchi, et al. (2012)

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