title: Third-line chemotherapy with carboplatin, gemcitabine and liposomised doxorubicin for malignant pleural mesothelioma.
abstract: There is no well-defined standard third-line chemotherapy for advanced malignant pleural mesothelioma (MPM). However, combination of carboplatin, liposomised doxorubicin (Caelyx) and gemcitabine (CCG regimen) has revealed noteworthy activity when used as first-line treatment. The aim of this study is to assess efficacy and toxicity profile for patients with MPM receiving CCG regimen as a third-line treatment. Carboplatin (AUC 5), Caelyx (30 mg/m(2)) and Gemcitabine (1,000 mg/m(2)) day 1, together with Gemcitabine (800 mg/m(2)) day 8, were given in up to six cycles. Patients were unresectable, PS 0-2, and had previously received a first-line platinum-based regimen and either vinorelbine or pemetrexed as second line. Response to treatment was assessed by CT scan using Modified RECIST criteria for mesothelioma. Forty-three patients were treated between 2010 and 2014. Median age was 67 years (47-82), 72 % males, and 79 % had previous asbestos exposure. Ninety per cent had PS 0-1, 58 % had epitheloid subtype and 63 % IMIG stage IV. First-line treatment was platinum and pemetrexed in 42 cases. Second-line treatment was vinorelbine in 42 cases and pemetrexed in one patient. Median lead time from cessation of second-line treatment to start of third CCG was 1 month. Twenty-eight per cent of the patients received six cycles, while treatment was postponed due to toxicities, mainly haematological, in 56 % of cases. No toxicity-related deaths occurred. Partial response (PR) occurred in 14 %, and disease control rate (DCR) was 60 %. Medians of overall survival (OS) from diagnosis and from start of CCG treatment were 25.2 months (18.4-31.5 months) and 6.8 months (5.4-8.4 months), respectively. Progression-free survival (PFS) was 4.1 months (1.7-4.5 months). Third-line CCG revealed a noteworthy efficacy with a DCR of 60.4 %. It was, however, associated with considerable haematological toxicity. Less toxic and more active treatment options are clearly needed.
authors.affiliation: Department of Oncology, Finsen Centre/National University Hospital, Rigshospitalet/Copenhagen University Hospital, 9 Blegdamsvej, 2100, Copenhagen Ø, Denmark, viniciusablima@gmail.com.
authors.forename: Vinicius Araújo B
authors.initials: VA
authors.lastname: de Lima
authors.forename: Jens Benn
authors.initials: JB
authors.lastname: Sørensen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D018301:Neoplasms, Mesothelial / Q000188:drug therapy* / Q000401:mortality; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011092:Polyethylene Glycols / Q000008:administration & dosage; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D000093542:Gemcitabine
chemical_list: C506643:liposomal doxorubicin; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D016190:Carboplatin; D000093542:Gemcitabine