Phase II trial of intravenous endotoxin in patients with colorectal and non-small cell lung cancer.
We report the immunological and clinical results of a phase II trial with intravenously administered highly purified endotoxin (Salmonella abortus equi) in patients with advanced cancer. 15 patients with non-small cell lung cancer and 27 with colorectal cancer were entered into the study. 37 evaluable patients received at least four injections of endotoxin (4 ng/kg body weight) and 1600 mg ibuprofen orally in 2-week intervals. Transient renal (WHO grade 0-1) and hepatic (WHO grade 0-4) toxicities occurred in several patients. Constitutional side-effects such as fever, chills and hypotension could not be prevented completely by pretreatment with ibuprofen. 3 patients in the colorectal cancer group demonstrated objective responses (1 complete remission (CR), 2 partial remission (PR)). The complete remission has been maintained for more than 3 years, while the partial remissions were stable for 7 and 8 months, respectively. Only marginal antitumour effects were seen in the lung cancer group. Tolerance of the macrophage system to the stimulatory effect of endotoxin, as measured by human necrosis factor alpha (TNF-alpha) release into serum, built up after the first administration and remained at a steady-state level after each subsequent injection. In constrast, rising CD4:CD8 ratio and release of tumour necrosis factor beta (TNF-beta) indicated the continuing activation of the lymphocyte system by repetitive injections of endotoxin.
Otto
F
F
Medizinische Klinik I der Albert-Ludwig-Universität, Germany.
Schmid
P
P
Mackensen
A
A
Wehr
U
U
Seiz
A
A
Braun
M
M
Galanos
C
C
Mertelsmann
R
R
Engelhardt
R
R
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000628:therapy*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000097:blood; D004731:Endotoxins / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use; D007958:Leukocyte Count / Q000187:drug effects; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D016131:Lymphocyte Subsets / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001427:Bacterial Toxins; D016207:Cytokines; D004731:Endotoxins; C027952:salmonella toxin; D007052:Ibuprofen