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

Our plain-English summary of A randomized phase II study of SRL172 (Mycobacterium vaccae) combined with chemotherapy in patients with advanced inoperable non-small-cell lung cancer and mesothelioma, by M.E. O'Brien, A. Saini, I.E. Smith, et al (British Journal of Cancer, 2000).

The study

• Authors: M.E. O'Brien, A. Saini, I.E. Smith, A. Webb, K. Gregory, R. Mendes, C. Ryan, K. Priest, K.V. Bromelow, R.D. Palmer, N. Tuckwell, D.A. Kennard, B.E. Souberbielle
• Journal: British Journal of Cancer
• Published: 2000;83(7):853-7
• Type of article: Randomized trial
• Cited by: 64 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

Copyright 2000 Cancer Research Campaign.

In plain English

This was a small randomized phase II trial at the Royal Marsden Hospital and the Kent Cancer Centre. It tested heat-killed Mycobacterium vaccae (SRL172), injected into the skin, alongside chemotherapy with mitomycin C, vinblastine and cisplatin. Patients had untreated, symptomatic, advanced inoperable non-small-cell lung cancer (NSCLC) or mesothelioma. Of 29 patients, 9 had mesothelioma. Fifteen received chemotherapy alone and 14 received chemotherapy plus SRL172. Toxicity was comparable between the groups. SRL172 caused induration at the injection site, and there was one treatment-related death in the combined group. Among the 28 evaluable patients, the combined group showed a trend towards a higher response rate (54% vs. 33%, P = 0.3) and longer median survival (9.7 vs. 7.5 months, P = 0.235). More of them were alive at one year (42% vs. 18%). Among mesothelioma patients, 2 of 4 had a partial response with the combination, compared with 1 of 5 with chemotherapy alone. Appetite appeared better with SRL172 (P = 0.01). The authors concluded that the results suggest a benefit, and a phase III trial was underway.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Randomized phase II clinical trial comparing chemotherapy alone with chemotherapy plus SRL172
• Who was studied: 29 previously untreated patients with symptomatic NSCLC (20) or mesothelioma (9), treated at the Royal Marsden Hospital and the Kent Cancer Centre. There were 20 men and 9 women, with a median age of 60 years (range 33 to 71). Most had stage IIIB or IV disease. 28 patients were evaluable; one patient in the combined arm was not eligible.
• Exposure: Not an asbestos exposure study. The treatment studied was mitomycin C, vinblastine and cisplatin chemotherapy every 3 weeks (maximum 6 courses), given alone or with intradermal injections of heat-killed Mycobacterium vaccae (SRL172). The injections were given monthly for the first 3 doses, then every 3 to 6 months. No asbestos exposure data were reported for the patients.
• Main results:
  • Among the 28 patients evaluable for response, the chemotherapy plus SRL172 group showed a trend towards a higher response rate (54% vs. 33%, P = 0.3) and longer median survival (9.7 months vs. 7.5 months, P = 0.235) than chemotherapy alone.
  • On intention-to-treat analysis, median survival was 9.4 months with chemotherapy plus SRL172 vs 7.5 months with chemotherapy alone (P = 0.3).
  • The proportion of treated patients alive at one year was 42% in the combined group vs. 18% in the chemotherapy-alone group.
  • Among mesothelioma patients, 2 of 4 had a partial response in the combination group, compared with 1 of 5 in the chemotherapy-alone group.
  • Apart from induration at the injection site, SRL172 caused no treatment-related toxicity. There was one treatment-related death in the combined group.
  • SRL172 appeared to improve sleep (P = 0.08) and poor appetite (P = 0.01).
  • In the combined arm, two patients later underwent potentially curative surgery and one patient had radical radiotherapy.
  • Baseline serum TNF-alpha was lower in responders (mean 37.9 pg/ml) than in non-responders (mean 45.8 pg/ml), P = 0.01. After correction for the number of comparisons, the P value was 0.14, which was not significant.
• The authors' conclusion: The authors concluded that the results suggest a benefit from combining intravenous chemotherapy with intradermal SRL172 in patients with lung cancer. They reported that this led to a larger phase III randomized trial in non-small-cell lung cancer.
• Limitations the authors state:
  • Full quality of life assessment was not analysed because few patients returned repeat questionnaires.
  • Only serum cytokines were measured. Changes could have been missed because of the timing of the assay or the assay's lack of sensitivity.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Chemotherapy, Lung Cancer, Mesothelioma, Non-Small Cell Lung Cancer, Inflammation, Median Overall Survival, Cytokine.

Related studies

• Sunitinib combined with pemetrexed and cisplatin: results of a phase I dose-escalation and pharmacokinetic study in patients with advanced solid malignancies, with an expanded cohort in non-small cell lung cancer and mesothelioma — D.R. Camidge, N. Blais, et al. (2013)
• Cutaneous toxicity after intradermal vaccination with Mycobacterium vaccae against lung cancer and malignant mesothelioma — H.S. Pandha, P. Mortimer, et al. (2001)
• Randomised phase II study of cisplatin-etoposide versus infusional carboplatin in advanced non-small-cell lung cancer and mesothelioma — S.C. White, H. Anderson, et al. (2000)
• A Prospective Phase II Single-arm Study of Niraparib Plus Dostarlimab in Patients With Advanced Non-small-cell Lung Cancer and/or Malignant Pleural Mesothelioma, Positive for PD-L1 Expression and Germline or Somatic Mutations in the DNA Repair Genes: Rationale and Study Design — F. Passiglia, P. Bironzo, et al. (2021)
• Mathematical modeling for Phase I cancer trials: A study of metronomic vinorelbine for advanced non-small cell lung cancer (NSCLC) and mesothelioma patients — F. Barlesi, D.C. Imbs, et al. (2017)
• Sunitinib combined with pemetrexed and carboplatin in patients with advanced solid malignancies--results of a phase I dose-escalation study — N. Blais, D.R. Camidge, et al. (2013)

Browse more research in British Journal of Cancer, or return to medical research.