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

Mycobacterial preparations have been used with limited success against canc er apart from superficial bladder cancer. Recently, a therapeutic vaccine d erived from Mycobacterium vaccae has been given to patients with prostate c ancer and melanoma indicating a possible beneficial effect on disease activ ity in such patients. We have recently initiated a series of randomized stu dies to test the feasibility and toxicity of combining a preparation of hea t-killed Mycobacterium vaccae (designated SRL172) with a multidrug chemothe rapy regimen to treat patients with inoperable non-small cell lung cancer ( NSCLC) and mesothelioma. 28 evaluable patients with previously untreated sy mptomatic NSCLC and mesothelioma were randomized to receive either 3 weekly intravenous combination chemotherapy alone, or chemotherapy given with mon thly intra-dermal injections of SRL172. Safety and tolerability were scored by common toxicity criteria and efficacy was evaluated by survival of pati ents and by tumour response assessed by CT scanning. The toxicity of chemot herapy was similar in the two groups. SRL172 caused mild inflammation at th e injection site. In the group of patients randomized to receive chemothera py combined with SRL172, there was a trend towards improved response rate ( 54% vs, 33%) with more patients in the combined arm receiving radical surge ry and radiotherapy, improved median survival (9.7 months vs. 7.5 months) a nd 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 chang e in serum cytokine levels for gamma-interferon and TNF-alpha before and af ter treatment. in patients with NSCLC and mesothelioma, there may be a bene ficial interaction when chemotherapy is administered in combination with SR L172. Confirmation of this effect and further investigation is underway in a randomized phase III trial and in laboratory models. (C) 2000 Cancer Rese arch Campaign.