Human tumor cells have markedly elevated activity of enzymes of the purine and pyrimidine de novo and salvage pathways. Our therapy protocol is based on these findings. Different antimetabolites (MTX, 5-FU, dFdC, AZT) were administered to hit key enzymes. Vindesine and ifosfamide were aimed to block macromolecules. Repair mechanisms were impaired by hydroxyurea and topotecan. DNA transcription was blocked by actinomycin. IFNs (alpha, gamma) and IL-2 served as immuno-modulators. 47 patients (age 61.5 years, Karnowsky score 85%) were treated in an out-patient-setting. Median number of cycles was 3. General toxicity was low. Leucocytes, platelets, and monocytes were significantly reduced during therapy, but returned to normal on day 29. Lymphocyte subtypes did not show significant changes. 3 complete clinical responses, 22 partial responses, 9 progressive diseases were observed. CR occurred in 1/4 patients with kidney, in 1/1 with bladder, and in 1/5 with breast cancer.

Aged↗

PubMedDate not supplied

Long-term results with FAMTX (5-fluorouracil, adriamycin, methotrexate) in advanced gastric cancer.

In a phase II trial we tried to evaluate the efficacy of a sequential combination of high-dose (HD) MTX and 5-FU combined with Adriamycin (ADM). In a pilot study we found HDMTX effective as a single agent in gastric cancer. MTX and 5-FU were combined sequentially because Cadman and Bertino had shown synergism for this combination. The treatment protocol consisted of HDMTX, 1.5 g/m2 of body surface, and HD5-FU, 1.5 g/m2. MTX was administered 1 hour prior to 5-FU. Both drugs were given as a bolus. 24 hours after MTX administration, citrovorum factor rescue was started, 15 mg/m2, q6h x 12, orally. 48 hours after MTX administration, the serum concentration of the drug was measured by HPLC. 14 days after MTX was given, ADM, 30 mg/m2, was injected as a bolus. This protocol was repeated every 28 days. Patients eligible for this treatment were required to have a creatinine clearance of greater than 60 ml/min. 116 patients with metastasized gastric cancer and a performance status between 40 and 70% were treated. The response rate was 58% (67/116 patients). 14/116 patients (12%) had complete remission. The median survival probability for all patients was 9 months, for responders 15 months, while for patients with complete response it has not been reached. The median survival for nonresponders was only 4 months. Around 10% of all patients lived longer than 6 years. The median follow-up-time was 4 years. Cytostatic treatment was relatively well tolerated. The deaths of 3 patients were drug-related. A quarter of all patients could be treated on an outpatient basis.

Adenocarcinoma↗