title: Combined-modality treatment of inoperable lung cancer (i.v. immunotherapy, chemotherapy, and radiotherapy).
abstract: Patients with inoperable non-small cell carcinoma of the bronchus were treated by iv methanol extraction residue of bacillus Calmette-Guérin (MER) followed by combination chemotherapy with methotrexate, doxorubicin, cyclophosphamide, and lomustine (MACC). Radiotherapy was added in patients with localized disease. MER was given iv in four weekly courses. The dose ranged between 0.1 and 0.8 mg/m2/course and was determined according to the skin reactivity to MER. None of the 19 patients treated with iv MER had an objective tumor response during immunotherapy. Five of 16 evaluable patients receiving MACC (31%) achieved partial response. The overall median survival for all 17 patients treated was 11 months according to the protocol. During immunotherapy the following side effects were observed: all patients had fever and chills and most had malaise, nausea and/or vomiting, and headache. Transient abnormalities of liver function tests were found in six patients, and in one patient roentgenographic changes suggestive of lung granulomas were seen. The side effects were more severe during the first course than in the further treatments. Side effects of the MACC combination were comparable to those observed in previously reported studies. Immunological monitoring performed during immunotherapy revealed that iv MER had an unfavorable effect on the immune system. Following four courses there was a decrease in the in vivo skin reactivity to MER and to five recall antigens. Twenty-four hours after the initiation of iv MER there was a tendency for decrease in the lymphoproliferation to phytohemagglutinin, an increase in the indices of the adherent cell suppressor system and the prostaglandin-related suppressor system, and an increase in the percentage of adherent mononuclear cells. No consistent changes in serum lysozyme were found. A transient increase in the total number of peripheral blood leukocytes and a decrease in the number of lymphocytes were noticed 24 hours after iv MER. Taking into account the results of the immunological studies and the overall therapeutic results, we do not feel justified in continuing to use this combined modality treatment.
authors.forename: E
authors.initials: E
authors.lastname: Robinson
authors.forename: N
authors.initials: N
authors.lastname: Haim
authors.forename: R
authors.initials: R
authors.lastname: Segal
authors.forename: Z
authors.initials: Z
authors.lastname: Veseley
authors.forename: T
authors.initials: T
authors.lastname: Mekori
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality / Q000628:therapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000276:immunology / Q000401:mortality / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007957:Leukocyte Adherence Inhibition Test; D008130:Lomustine / Q000008:administration & dosage / Q000009:adverse effects; D008175:Lung Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008213:Lymphocyte Activation; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011879:Radiotherapy Dosage; D012882:Skin Tests; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D001500:BCG Vaccine; C011499:methanol extraction residue (MER) tubercle bacillus fraction; D008130:Lomustine; D004317:Doxorubicin; D003520:Cyclophosphamide; D008727:Methotrexate