A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma.

1994 ◽  
Vol 12 (6) ◽  
pp. 1156-1163 ◽  
Author(s):  
V Rusch ◽  
L Saltz ◽  
E Venkatraman ◽  
R Ginsberg ◽  
P McCormack ◽  
...  
Keyword(s):  
Overall Survival ◽  
Malignant Pleural Mesothelioma ◽  
Systemic Chemotherapy ◽  
Survival Duration ◽  
Pleural Mesothelioma ◽  
Computed Tomographic ◽  
Novel Approach ◽  
Intrapleural Chemotherapy ◽  
Grade 3 ◽  
Better Than

PURPOSE This study investigated the feasibility of a novel approach to the treatment of malignant pleural mesothelioma by combining surgical resection with immediate postoperative intrapleural chemotherapy and subsequent systemic chemotherapy. PATIENTS AND METHODS Patients with biopsy-proven, resectable malignant pleural mesothelioma underwent pleurectomy/decortication immediately followed by intrapleural chemotherapy with cisplatin 100 mg/m2 and mitomycin 8 mg/m2. Systemic chemotherapy was started 3 to 5 weeks postoperatively and included cisplatin 50 mg/m2 on days 1, 8, 15, 22, 36, 43, 50, and 57, and mitomycin 8 mg/m2 on days 1 and 36. Patients were then monitored by serial chest and abdominal computed tomographic (CT) scans every 3 months until death or for a minimum of 18 months, whichever occurred first. RESULTS Of 36 patients entered onto the study, 28 had pleurectomy/decortication and intrapleural chemotherapy. There was one postoperative death, and two episodes of grade 4 renal toxicity after intrapleural chemotherapy. The 23 patients who also had systemic chemotherapy received a median of 80% and 87% of the planned total cisplatin and mitomycin doses, respectively. No grade 3 or 4 toxicities were observed. The overall survival rate of the 27 patients who were originally candidates for systemic chemotherapy was 68% at 1 year and 40% at 2 years, with a median survival duration of 17 months. Locoregional disease was the most common form of relapse (16 of 20 patients). CONCLUSION This short but aggressive combined modality regimen was generally well tolerated, but should not be used outside of a protocol setting because of the potential for serious toxicity. Overall survival was as good or better than with previously reported multimodality approaches, but other strategies are needed to improve local control.

Phase II Study of Pemetrexed Plus Carboplatin in Malignant Pleural Mesothelioma

2006 ◽  
Vol 24 (9) ◽  
pp. 1443-1448 ◽  
Author(s):  
Giovanni L. Ceresoli ◽  
Paolo A. Zucali ◽  
Adolfo G. Favaretto ◽  
Francesco Grossi ◽  
Paolo Bidoli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disease Control ◽  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Objective Response ◽  
Dose Intensity ◽  
Pleural Mesothelioma ◽  
Standard Regimen ◽  
Time Curve ◽  
Grade 3

Purpose This multicenter, phase II clinical study was conducted to evaluate the activity of the combination of pemetrexed and carboplatin in patients with malignant pleural mesothelioma (MPM). Patients and Methods Chemotherapy-naive patients with measurable disease and adequate organ function, who were not eligible for curative surgery, received pemetrexed 500 mg/m2 and carboplatin area under the plasma concentration-time curve of 5 mg/mL/min, administered intravenously every 21 days. All patients received folic acid and vitamin B12 supplementation. Pemetrexed was provided within the Expanded Access Program. Results A total of 102 patients were enrolled. An objective response was achieved in 19 patients (two complete and 17 partial responses), for a response rate of 18.6% (95% CI, 11.6% to 27.5%). Forty-eight patients (47.0%; 95% CI, 37.1% to 57.2%) had stable disease after treatment. Overall, 67 patients (65.7%) achieved disease control (95% CI, 55.6% to 74.8%). Median time to progression was 6.5 months; median overall survival time was 12.7 months. Compliance to treatment was excellent, with a relative dose-intensity of 97% for pemetrexed and 98% for carboplatin. Toxicity was mild, with grade 3 or 4 neutropenia occurring in 9.7% of total cycles and grade 3 or 4 anemia occurring in 3.5% of total cycles. Nonhematologic toxicity was negligible. Conclusion Treatment with pemetrexed and carboplatin was active and well tolerated in patients with MPM. Disease control rate, time to disease progression, and overall survival were similar to the results achieved with the standard regimen of pemetrexed and cisplatin, suggesting that the carboplatin combination could be an alternative option for these patients.

Phase II Study of Pemetrexed With and Without Folic Acid and Vitamin B12 as Front-Line Therapy in Malignant Pleural Mesothelioma

2003 ◽  
Vol 21 (8) ◽  
pp. 1556-1561 ◽  
Author(s):  
Giorgio V. Scagliotti ◽  
Dong-M. Shin ◽  
Hedy L. Kindler ◽  
Michael J. Vasconcelles ◽  
Uwe Keppler ◽  
...  
Keyword(s):  
Overall Survival ◽  
Folic Acid ◽  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Median Overall Survival ◽  
Single Agent ◽  
Vitamin Supplementation ◽  
Vitamin B ◽  
Pleural Mesothelioma ◽  
Grade 3

Purpose: This phase II clinical study evaluated the efficacy of pemetrexed for the treatment of malignant pleural mesothelioma (MPM). Patients and Methods: Patients with a histologically proven diagnosis of MPM, chemotherapy-naive measurable lesions, and adequate organ function received pemetrexed (500 mg/m2) intravenously over 10 minutes every 3 weeks. After a protocol change, most patients also received folic acid and vitamin B12 supplementation to improve safety. Results: A total of 64 patients were enrolled. Nine (14.1%) of the 64 patients had a partial response. The Kaplan-Meier estimate for median overall survival was 10.7 months. Forty-three patients received vitamin supplementation for all courses of therapy, and 21 patients did not. Seven of the nine responders were vitamin supplemented. The median overall survival was 13.0 months for supplemented patients and 8.0 months for nonsupplemented patients. Vitamin-supplemented patients completed more cycles of therapy than nonsupplemented patients (median, six v two cycles, respectively). Grade 3/4 neutropenia (23.4%) and grade 3/4 leukopenia (18.8%) were the most common laboratory toxicities. Fatigue and febrile neutropenia were the most commonly reported nonlaboratory events (grade 3, 6.3%; grade 4, 0.0% each). The incidence of these toxicities was generally lower in the supplemented patients. Conclusion: Single-agent pemetrexed for MPM resulted in a moderate response rate (14.1%) and median overall survival of 10.7 months. Patients supplemented with folic acid and vitamin B12 tolerated treatment better (less toxicity and more cycles of treatment) and had a 5-month greater median overall survival than nonsupplemented patients. These results indicate that patients with MPM could benefit from single-agent pemetrexed treatment combined with vitamin supplementation.

scholarly journals Radical Hemithoracic Radiotherapy Induces Systemic Metabolomics Changes That Are Associated with the Clinical Outcome of Malignant Pleural Mesothelioma Patients

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 508
Author(s):  
Emanuela Di Gregorio ◽  
Gianmaria Miolo ◽  
Asia Saorin ◽  
Elena Muraro ◽  
Michela Cangemi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Overall Survival ◽  
Clinical Outcome ◽  
Malignant Pleural Mesothelioma ◽  
Therapeutic Option ◽  
Enrichment Analysis ◽  
Metabolic Effects ◽  
Pleural Mesothelioma ◽  
Polyamine Biosynthesis ◽  
The Individual

Radical hemithoracic radiotherapy (RHRT) represents an advanced therapeutic option able to improve overall survival of malignant pleural mesothelioma patients. This study aims to investigate the systemic effects of this radiotherapy modality on the serum metabolome and their potential implications in determining the individual clinical outcome. Nineteen patients undergoing RHRT at the dose of 50 Gy in 25 fractions were enrolled. Serum targeted metabolomics profiles were investigated at baseline and the end of radiotherapy by liquid chromatography and tandem mass spectrometry. Univariate and multivariate OPLS-DA analyses were applied to study the serum metabolomics changes induced by RHRT while PLS regression analysis to evaluate the association between such changes and overall survival. RHRT was found to affect almost all investigated metabolites classes, in particular, the amino acids citrulline and taurine, the C14, C18:1 and C18:2 acyl-carnitines as well as the unsaturated long chain phosphatidylcholines PC ae 42:5, PC ae 44:5 and PC ae 44:6 were significantly decreased. The enrichment analysis showed arginine metabolism and the polyamine biosynthesis as the most perturbed pathways. Moreover, specific metabolic changes encompassing the amino acids and acyl-carnitines resulted in association with the clinical outcome accounting for about 60% of the interpatients overall survival variability. This study highlighted that RHRT can induce profound systemic metabolic effects some of which may have a significant prognostic value. The integration of metabolomics in the clinical assessment of the malignant pleural mesothelioma could be useful to better identify the patients who can achieve the best benefit from the RHRT treatment.

Intrapleural cisplatin and mitomycin for malignant mesothelioma following pleurectomy: pharmacokinetic studies.

1992 ◽  
Vol 10 (6) ◽  
pp. 1001-1006 ◽  
Author(s):  
V W Rusch ◽  
D Niedzwiecki ◽  
Y Tao ◽  
C Menendez-Botet ◽  
A Dnistrian ◽  
...  
Keyword(s):  
Pleural Fluid ◽  
Malignant Pleural Mesothelioma ◽  
Plasma Levels ◽  
Peak Plasma ◽  
Systemic Absorption ◽  
Pharmacokinetic Studies ◽  
Logarithmic Scale ◽  
Pleural Mesothelioma ◽  
Intrapleural Chemotherapy ◽  
The Mean

PURPOSE Intrapleural cisplatin-based chemotherapy has been used in the treatment of patients with malignant pleural mesothelioma and malignant pleural effusions, but the pharmacokinetics of this form of chemotherapy have not been previously evaluated. We performed pharmacokinetic studies on 12 patients who received both intrapleural cisplatin and mitomycin immediately following pleurectomy/decortication for malignant pleural mesothelioma. PATIENTS AND METHODS Simultaneous pleural fluid and plasma samples were collected at 15 and 30 minutes, and at 1, 2, 3, 4, and 24 hours after administration of the intrapleural chemotherapy (cisplatin 100 mg/m2 and mitomycin 8 mg/m2), and after cisplatin (total and free) and mitomycin levels were measured. The mean peak levels, the areas under the concentration-time curve (AUC) and the drug half-lives (t1/2s) in plasma and pleural fluid were compared using the paired t test. Differences were considered significant if P less than or equal to .05. RESULTS Systemic absorption was rapid, with peak plasma levels being reached within 1 hour of administration of the intrapleural chemotherapy. Peak plasma levels measured after intrapleural chemotherapy approximated those reportedly attained during systemic administration of these drugs at similar doses. However, the mean peak cisplatin and mitomycin levels, and their mean AUCs, were significantly higher in the pleural fluid than in the plasma. There was a three- to fivefold advantage (on a logarithmic scale) for pleural to plasma AUCs for both cisplatin and mitomycin. The mean t1/2s for cisplatin and mitomycin were significantly longer in the plasma than in the pleural fluid. CONCLUSIONS The pharmacokinetics of intrapleural cisplatin-based chemotherapy are analogous to those of intraperitoneal chemotherapy. Our findings show that intrapleural cisplatin-based chemotherapy has a distinct local pharmacologic advantage, but also produces significant and sustained drug plasma levels.

scholarly journals Genetic alterations of malignant pleural mesothelioma: association with tumor heterogeneity and overall survival

2020 ◽  
Vol 14 (6) ◽  
pp. 1207-1223 ◽  
Author(s):  
Lisa Quetel ◽  
Clément Meiller ◽  
Jean‐Baptiste Assié ◽  
Yuna Blum ◽  
Sandrine Imbeaud ◽  
...  
Keyword(s):  
Overall Survival ◽  
Malignant Pleural Mesothelioma ◽  
Tumor Heterogeneity ◽  
Genetic Alterations ◽  
Pleural Mesothelioma

scholarly journals OA13.03 Long-Term Overall Survival for Patients with Malignant Pleural Mesothelioma on Pembrolizumab Enrolled in KEYNOTE-028

2017 ◽  
Vol 12 (1) ◽  
pp. S294 ◽  
Author(s):  
Evan Alley ◽  
Juanita Lopez ◽  
Armando Santoro ◽  
Anne Morosky ◽  
Sanatan Saraf ◽  
...  
Keyword(s):  
Overall Survival ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma

scholarly journals External validation of prognostic indices for overall survival of malignant pleural mesothelioma

Lung Cancer ◽  
2017 ◽  
Vol 113 ◽  
pp. 88-92 ◽  
Author(s):  
Yuki Kataoka ◽  
Yosuke Yamamoto ◽  
Taiichiro Otsuki ◽  
Sawako Kaku ◽  
Nobuko Maehashi-Wada ◽  
...  
Keyword(s):  
Overall Survival ◽  
Malignant Pleural Mesothelioma ◽  
External Validation ◽  
Pleural Mesothelioma ◽  
Prognostic Indices

scholarly journals Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and Folate Antimetabolite Chemotherapy

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Mathieu D. Saint-Pierre ◽  
Christopher Pease ◽  
Hamid Mithoowani ◽  
Tinghua Zhang ◽  
Garth A. Nicholas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
Performance Status ◽  
Treatment Modalities ◽  
Pleural Mesothelioma ◽  
Cox Models ◽  
Platinum Based Chemotherapy ◽  
Before And After ◽  
Incremental Improvement

Introduction. Malignant pleural mesothelioma (MPM) is associated with a poor prognosis. Palliative platinum-based chemotherapy may help to improve symptoms and prolong life. Since 2004, the platinum is commonly partnered with a folate antimetabolite. We performed a review investigating if survival had significantly changed before and after the arrival of folate antimetabolites in clinical practice. Methods. All MPM patients from January 1991 to June 2012 were identified. Data collected included age, gender, asbestos exposure, presenting signs/symptoms, performance status, histology, stage, bloodwork, treatment modalities including chemotherapy, and date of death or last follow-up. The primary endpoint was overall survival. Cox models were applied to determine variables associated with survival. Results. There were 245 patients identified. Median overall survival for all patients was 9.4 months. After multivariate analysis, performance status, stage, histology, leucocytosis, and thrombophilia remained independently associated with survival. Among all patients who received chemotherapy, there was no difference in overall survival between the periods before and after folate antimetabolite approval: 14.2 versus 13.2 months (P=0.35). Specifically receiving combined platinum-based/folate antimetabolite chemotherapy did not improve overall survival compared to all other chemotherapy regimens: 14.1 versus 13.6 months (P=0.97). Conclusions. In this review, we did not observe an incremental improvement in overall survival after folate antimetabolites became available.

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