Thirty five previously untreated patients with small cell lung cancer older than 70 years were treated with oral etoposide (800 mg/m2 over five consecutive days) every four weeks. Twenty two patients had extensive disease and 13 limited disease. The overall response rate was 71%. The median survival for patients with limited diseases was 16 (range 6-32) months and for patients with extensive disease nine (range 4-17) months. There was mild haematological toxicity and alopecia but no major toxicity. It is concluded that etoposide in this dose regimen is an effective and well tolerated treatment for elderly patients with small cell lung cancer.
Immunobiologic parameters measured during a phase I trial of intravenously (i.v.) administered bispecific monoclonal antibodies (BsmAb) in renal cell carcinoma (RCC) patients are described. The BsmAb used, BIS-1, is reactive with a pancarcinoma-associated 38 kDa transmembrane glycoprotein, EGP-2, as well with the CD3 complex. Patients received during a 2 h i.v. infusion F(ab')2 fragments of BIS-1 at doses of 1, 3, or 5 μg/kg body weight during concomitantly applied subcutaneous (s.c.) IL-2 treatment. Acute but transient BIS-1 F(ab')2-related toxicity was observed at the 3 and 5 μg/kg dose level, and the maximum tolerated dose (MTD) was set at 5 μg/kg. A dose-dependent binding of BIS-1 F(ab')2 to circulating T lymphocytes was found. The in vivo occupancy of CD3 molecules on T lymphocytes was highest at the end of the infusion period and then rapidly decreased, as shown by flow cytometry. A much slower decrease of BIS-1 F(ab')2 binding was observed in vitro, suggesting migration of BIS-1 F(ab')2-loaded T lymphocytes from the circulation. A strong but transitory leukopenia was observed, in which LFA-1α bright, CD3/CD8 double positive T cells left the circulation preferentially. This phenomenon was most likely induced by elevated TNF-α and IFN-γ plasma levels, which were at a maximum shortly after the end of the infusion. Isolated peripheral blood mononuclear cells obtained from patients directly after treatment with BIS-1 F(ab')2 at the 3 and 5 μg/kg dose level showed increased EGP-2-directed antitumor activity.
A 54 year old woman presented with an intra-abdominal adenocarcinoma of primary coelomic origin and a syndrome of palmar fasciitis and arthritis, which was exacerbated during treatment by combination chemotherapy with intravenous carboplatin 300 mg/m2 and cyclophosphamide 750 mg/m2, while the tumour responded well.
