title: Clinical and immunological assessment of Mycobacterium vaccae (SRL172) with chemotherapy in patients with malignant mesothelioma.
abstract: The objectives of this study were to determine the toxicity of intratumoural/intrapleural SRL172 in addition to intradermal SRL172 and standard chemotherapy (mitomycin-C, vinblastine and cisplatin) in patients with malignant mesothelioma. Patients received chemotherapy (mitomycin-C: 8 mg m(-2), vinblastine: 6 mg m(-2), cisplatin 50 mg m(-2)) on a 3-weekly basis for up to six courses. IP SRL172 injections were given 3-weekly prior to chemotherapy and escalated in groups of three patients from 1 microg to 1 mg bacilli in 10-fold increments. Patients were also given ID SRL172 at a dose of 1 mg bacilli 4-weekly. Patients were assessed for toxicity after each course of chemotherapy and for response by CT imaging. Immuno-haematological parameters were analyzed pre-treatment and 1 month after completion of treatment. There was no dose limiting toxicity with IP SRL172 although there was greater toxicity at the highest dose (n=13). There were six out of 16 partial responses (37.5%). Haemato-immunological parameters, measured in seven patients pre and post-therapy, revealed that response rate correlated with a decrease in platelet count and there was an increase in activation of natural killer cells and a decrease in the percentage of IL-4 producing T cells in all tested patients post-treatment. SRL172 can be given safely into tumour deposits and the pleural cavity in patients with malignant mesothelioma and we have established the dose for phase II testing.
authors.affiliation: Lung Unit, Department of Haematology, The Royal Marsden Hospital NHS Trust, Downs Road, Sutton, SM2 5PT, UK.
authors.forename: R
authors.initials: R
authors.lastname: Mendes
authors.forename: M E R
authors.initials: ME
authors.lastname: O'Brien
authors.forename: A
authors.initials: A
authors.lastname: Mitra
authors.forename: A
authors.initials: A
authors.lastname: Norton
authors.forename: R K
authors.initials: RK
authors.lastname: Gregory
authors.forename: A R
authors.initials: AR
authors.lastname: Padhani
authors.forename: K V
authors.initials: KV
authors.lastname: Bromelow
authors.forename: A R
authors.initials: AR
authors.lastname: Winkley
authors.forename: S
authors.initials: S
authors.lastname: Ashley
authors.forename: I E
authors.initials: IE
authors.lastname: Smith
authors.forename: B E
authors.initials: BE
authors.lastname: Souberbielle
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001428:Bacterial Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009161:Mycobacterium; D009367:Neoplasm Staging; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D001428:Bacterial Vaccines; C451081:SRL172; D016685:Mitomycin; D014747:Vinblastine; D002945:Cisplatin