A randomized phase II study of SRL172 (Mycobacterium vaccae) combined with chemotherapy in patients with advanced inoperable non-small-cell lung cancer and mesothelioma

Br J Cancer. 2000 Oct;83(7):853-7. doi: 10.1054/bjoc.2000.1401.

Abstract

Mycobacterial preparations have been used with limited success against cancer apart from superficial bladder cancer. Recently, a therapeutic vaccine derived from Mycobacterium vaccae has been given to patients with prostate cancer and melanoma indicating a possible beneficial effect on disease activity in such patients. We have recently initiated a series of randomized studies to test the feasibility and toxicity of combining a preparation of heat-killed Mycobacterium vaccae (designated SRL172) with a multidrug chemotherapy regimen to treat patients with inoperable non-small cell lung cancer (NSCLC) and mesothelioma. 28 evaluable patients with previously untreated symptomatic NSCLC and mesothelioma were randomized to receive either 3 weekly intravenous combination chemotherapy alone, or chemotherapy given with monthly intra-dermal injections of SRL172. Safety and tolerability were scored by common toxicity criteria and efficacy was evaluated by survival of patients and by tumour response assessed by CT scanning. The toxicity of chemotherapy was similar in the two groups. SRL172 caused mild inflammation at the injection site. In the group of patients randomized to receive chemotherapy combined with SRL172, there was a trend towards improved response rate (54% vs. 33%) with more patients in the combined arm receiving radical surgery and radiotherapy, improved median survival (9.7 months vs. 7.5 months) and improved 1 year survival (42% vs. 18%). SRL172 appeared to improve sleep (P = 0.08) and improved appetite (P = 0.01). There was no detectable change in serum cytokine levels for gamma-interferon and TNF-alpha before and after treatment. In patients with NSCLC and mesothelioma, there may be a beneficial interaction when chemotherapy is administered in combination with SRL172. Confirmation of this effect and further investigation is underway in a randomized phase III trial and in laboratory models.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / adverse effects
  • Adjuvants, Immunologic / therapeutic use
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bacterial Vaccines / adverse effects
  • Bacterial Vaccines / immunology
  • Bacterial Vaccines / therapeutic use*
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Combined Modality Therapy
  • Female
  • Humans
  • Immunotherapy, Active
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / immunology
  • Lung Neoplasms / therapy*
  • Male
  • Mesothelioma / drug therapy
  • Mesothelioma / immunology
  • Mesothelioma / therapy*
  • Middle Aged
  • Mitomycin / administration & dosage
  • Mitomycin / adverse effects
  • Mycobacterium / immunology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Vaccines, Inactivated / adverse effects
  • Vaccines, Inactivated / immunology
  • Vaccines, Inactivated / therapeutic use
  • Vinblastine / administration & dosage
  • Vinblastine / adverse effects

Substances

  • Adjuvants, Immunologic
  • Bacterial Vaccines
  • Cancer Vaccines
  • Tumor Necrosis Factor-alpha
  • Vaccines, Inactivated
  • Interleukin-10
  • Mitomycin
  • Vinblastine
  • Interferon-gamma
  • Cisplatin