Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma

2017 ◽  
Vol 11 (8) ◽  
pp. 649-660 ◽  
Author(s):  
Giuseppe Marulli ◽  
Eleonora Faccioli ◽  
Alice Bellini ◽  
Marco Mammana ◽  
Federico Rea
Keyword(s):  
Adjuvant Therapy ◽  
Induction Chemotherapy ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma

scholarly journals Induction Chemotherapy Followed by Pleurectomy Decortication and Hyperthermic Intraoperative Chemotherapy (HITHOC) for Early-Stage Epitheliod Malignant Pleural Mesothelioma—A Prospective Report

2021 ◽  
Vol 10 (23) ◽  
pp. 5542
Author(s):  
Stefano Bongiolatti ◽  
Francesca Mazzoni ◽  
Ottavia Salimbene ◽  
Enrico Caliman ◽  
Carlo Ammatuna ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Malignant Pleural Mesothelioma ◽  
Early Stage ◽  
Disease Free Survival ◽  
Stage I ◽  
Long Term Results ◽  
Pleural Mesothelioma ◽  
Free Survival ◽  
Therapy Regimen ◽  
Platinum Based Chemotherapy

Malignant pleural mesothelioma (MPM) is an aggressive disease with poor prognosis and the current treatment for early-stage MPM is based on a multimodality therapy regimen involving platinum-based chemotherapy preceding or following surgery. To enhance the cytoreductive role of surgery, some peri- or intra-operative intracavitary treatments have been developed, such as hyperthermic chemotherapy, but long-term results are weak. The aim of this study was to report the post-operative results and mid-term outcomes of our multimodal intention-to-treat pathway, including induction chemotherapy, followed by surgery and Hyperthermic Intraoperative THOracic Chemotherapy (HITHOC) in the treatment of early-stage epithelioid MPM. Since 2017, stage I or II epithelioid MPM patients have been inserted in a surgery-based multimodal approach comprising platinum-based induction chemotherapy, followed by pleurectomy and decortication (P/D) and HITHOC with cisplatin. The Kaplan–Meier method was used to estimate overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). During the study period, n = 65 patients affected by MPM were evaluated by our institutional Multidisciplinary Tumour Board; n = 12 patients with stage I-II who had no progression after induction chemotherapy underwent P/D and HITHOC. Post-operative mortality was 0, and complications developed in n = 7 (58.3%) patients. The median estimated OS was 31 months with a 1-year and 3-year OS of 100% and 55%, respectively. The median PFS was 26 months with 92% of a 1-year PFS, whereas DFS was 19 months with a 1-year DFS rate of 83%. The multimodal treatment of early-stage epithelioid MPM, including induction chemotherapy followed by P/D and HITHOC, was well tolerated and feasible with promising mid-term oncological results.

Therapeutic targeting of polyamines in malignant pleural mesothelioma xenograft models.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20060-e20060
Author(s):  
James C. M. Ho ◽  
Sheng Yan ◽  
Sze Kwan Lam
Keyword(s):  
Adjuvant Therapy ◽  
Tumor Growth ◽  
Malignant Pleural Mesothelioma ◽  
Nude Mice ◽  
Pleural Mesothelioma ◽  
Term Survival ◽  
Early Stage Disease ◽  
Therapeutic Setting ◽  
Metastatic Setting ◽  
Humane Endpoint

e20060 Background: Although the use of asbestos has been restricted, the incidence of malignant pleural mesothelioma (MPM) is still rising. The US FDA approved a combination of pemetrexed with cisplatin for treatment of unresectable MPM. And development of novel adjuvant therapeutic options for resected early-stage disease is also urgently needed. From our preliminary data, ornithine decarboxylase (ODC) is highly expressed in MPM xenografts and clinical tumor samples. Upregulation of ODC increases polyamines production and enhances tumor growth. a-difluoromethylornithine (DFMO) is a specific ODC inhibitor. This study aims to disclose the adjuvant (minimal residual disease setting) and therapeutic (metastatic setting) effects of DFMO in MPM xenografts. Methods: In adjuvant therapy setting, nude mice were fed with DFMO in drinking water 7 days before subcutaneous inoculation of 200,000 tumor cells. In therapeutic setting, 107 corresponding cells were injected subcutaneously into nude mice which were randomized for treatment after established tumor growth. Mice with tumor size > 600mm3 were considered reaching humane endpoint. Spermidine levels, protein expression, cytokines concentration, and apoptosis were investigated by Dot plot, Western blot, ELISA, and TUNEL assay respectively. Results: In adjuvant therapy setting, DFMO suppressed tumor growth and increased median survival in both 211H and H226 xenografts. In H226 xenografts, 43% of treated mice have not yet reached humane endpoint, mimicking long-term survival. Upon DFMO treatment, decrease in spermidine level, increase in nitrotyrosine content, and activation of apoptosis were observed in both xenografts. In addition, increase in nitrosocysteine level, intratumoral IL-6, keratinocyte chemoattractant and TNFα, DNA lesions and inhibition of Akt/mTOR pathway were induced by DFMO in H226 xenografts, which may explain higher potency of DFMO in these xenografts. In therapeutic setting, DFMO also suppressed tumor growth in both xenografts with similar mechanisms. Conclusions: DFMO may have a potential role as adjuvant therapy in MPM especially epithelioid mesothelioma.

A feasibility study of induction pemetrexed plus cisplatin followed by pleurectomy/decortication for malignant pleural mesothelioma (Japan Mesothelioma Interest Group 1101 Trial).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8518-8518
Author(s):  
Seiki Hasegawa ◽  
Kohei Yokoi ◽  
Morihito Okada ◽  
Fumihiro Tanaka ◽  
Mototsugu Shimokawa ◽  
...  
Keyword(s):  
Surgical Technique ◽  
Pulmonary Function ◽  
Induction Chemotherapy ◽  
Malignant Pleural Mesothelioma ◽  
Primary Endpoint ◽  
Pulmonary Function Tests ◽  
Survival Rates ◽  
Extrapleural Pneumonectomy ◽  
Pleural Mesothelioma ◽  
Acceptable Risks

8518 Background: Although pleurectomy/decortication (P/D) has become a preferred surgical technique for malignant pleural mesothelioma (MPM), only a few prospective, multi-center clinical trials have been conducted. Here we present final results of a nationwide, prospective, multi-institutional study to evaluate the feasibility of induction chemotherapy followed by P/D. Methods: Eligibility criteria: a histologically confirmed diagnosis of MPM; clinical T1–3, N0–2, M0 disease; no prior treatment for the disease; age between 20 and 75 years; ECOG performance status of 0 or 1; and written informed consent. Treatment methods: Induction chemotherapy of pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 for 3 cycles, followed by P/D. Intraoperative conversion from P/D to extrapleural pneumonectomy (EPP) was permitted. Pulmonary function tests were performed at 3, 6, 12, 24, and 36 months after surgery. Primary endpoint was macroscopic complete resection (MCR) rate regardless of the surgical technique. Results: Of 24 patients enrolled, 20 patients were eligible: median age 66 (48–74); M/F: 17/3, Clinical stage I/II/III: 8/9/3; Histology epi/sar/bi: 19/1/0. Two discontinued protocol before surgery due to deteriorated FEV1 or adverse effect (AE) of chemotherapy, and the remaining 18 patients completed surgery with MCR: P/D in 15 patients and EPP in 3. The trial met the primary endpoint with MCR rate of 90% (18/20). There was no treatment-related 30- and 90-day mortality. There were two cases of chemotherapy-related grade 4 AEs, but no surgery-related grade 4 AE occurred. The overall survival rates at 1 and 2 years and median survival time (MST) after registration were 95.0% (95% CI, 69.5 to 99.3), 70.0% (45.1 to 85.3), and 41.4 months (19.7 to NA), respectively. The progression-free survival rates at 1 and 2 years and MST after registration were 84.7% (60.0 to 94.8), 42.4% (20.5 to 62.7), and 22.9 months (12.7 to 28.4), respectively. Recurrence occurred in 17 patients, and initial relapse sites were local in 17 (100%) and distal in 6 (35.3%). The best values of FVC and FEV1 during postoperative period were 78.0% and 82.5% of preoperative values, respectively. Conclusions: Induction chemotherapy plus P/D yielded a MST over 40 months with acceptable risks. Postoperative pulmonary function was approximately 80% of preoperative value. Clinical trial information: UMIN000009092.

Impact of induction chemotherapy and adjuvant radiation therapy on outcome after extrapleural pneumonectomy for malignant pleural mesothelioma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7708-7708 ◽  
Author(s):  
M. de Perrot ◽  
R. Feld ◽  
M. Anraku ◽  
A. Bezjak ◽  
R. Burkes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Induction Chemotherapy ◽  
Malignant Pleural Mesothelioma ◽  
Disease Free Survival ◽  
Extrapleural Pneumonectomy ◽  
High Dose ◽  
Pleural Mesothelioma ◽  
Free Survival ◽  
Disease Free

7708 Background: Examine the results of tri-modality therapy for malignant pleural mesothelioma (MPM). Methods: Protocol consisted of induction cisplatin-based chemotherapy, followed by extrapleural pneumonectomy (EPP) and adjuvant hemithoracic radiation therapy (RT) to 54 Gy. Results: A total of 60 patients were suitable candidates for tri-modality therapy between 01/2001 and 01/2007. Induction chemotherapy was administered to 56 patients; 4 patients underwent EPP without induction chemotherapy because of patient refusal (n=2), previous chemotherapy (n=1) and sarcomatoid MPM (n=1). Chemotherapy included vinorelbine/cisplatin (n=26), pemetrexed/cisplatin (n=26) and gemcitabine/cisplatin (n=4). EPP was performed in 47 patients; 13 patients did not undergo EPP because of tumor progression during chemotherapy (n=2), extensive chest wall involvement at surgery (n=6), or involvement of mediastinal lymph nodes at mediastinoscopy (n=5). Three patients (6%) died within 30 days of surgery. Pathological stage was II (n=6), III (n=35), and IV (n=6). Adjuvant RT was administered postoperatively to 36 patients and is ongoing in 5 patients; 6 patients did not receive adjuvant RT because of fatigue (n=5) or previous RT (n=1), and 4 patients did not complete RT up to 54 Gy. Overall survival for the 23 patients who completed the tri-modality therapy was 37% at 3 years with a median survival of 15 months. Eleven of the 23 patients had recurrence after a median of 8 months (range, 2–13 months). Recurrences were locoregional (n=2), in contralateral chest (n=3), abdomen (n=3), contralateral chest and abdomen (n=2), or pericardium (n=1). Among patients undergoing EPP, disease-free survival was longer in patients undergoing adjuvant high dose hemithoracic RT (p=0.07), in epithelial tumors (p=0.03), and in early stage (p=0.07). Overall survival was influenced by histology (p=0.007) and stage (p=0.05), but not by adjuvant high dose hemithoracic RT (p=0.5). The type of chemotherapy had no impact on disease-free and overall survival. Conclusions: Aggressive tri-modality therapy is feasible in selected patient with MPM. Adjuvant high dose hemithoracic RT can improve disease free survival and achieve good local control. No significant financial relationships to disclose.

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