Mitoxantrone, fluorouracil, and L-folinic acid in anthracycline-pretreated metastatic breast cancer patients.

In this phase II trial we have evaluated the activity and toxicity of a combination regimen containing mitoxantrone, L-leucovorin, and fluorouracil in patients with advanced breast cancer pretreated with anthracyclines. Forty-six patients were included into the study; they received a total of 227 cycles of chemotherapy. Median age was 63 years (range 34-78), median performance status was 80 (range 60-100). Visceral metastases were present in 37 patients, 6 patients had bone involvement only, while 3 patients had soft tissue/lymph node disease. Median number of previous chemotherapy regimens for advanced disease was 2 (range 1-3). Ten patients had anthracycline primary resistance (progressive disease during treatment). Twenty-three patients received mitoxantrone 12 mg/sqm day 1; fluorouracil 370 mg/sqm and L-folinic acid 100 mg/sqm days 1-3 administered every three weeks. Another group of 23 patients were treated with the same regimen using a prolonged 5FU/L-FA schedule (5 days). Two complete responses and 6 partial responses were recorded with the 3-day schedule; 7 partial responses in the 5-day schedule (overall response rate 32.6%, 95% C.I. 19-46%). Two partial responses were observed in patients with anthracycline primary resistance. Median response duration was 9 months (range 3-16). Hematologic toxicity was mild: grade 3-4 leukopenia was recorded in 5 patients, grade 3-4 thrombocytopenia in 3 patients. Grade III-IV stomatitis and diarrhea was recorded in 4 and 5 patients respectively (all receiving the 5-day 5-FU/L-FA schedule). Cardiac toxicity was observed in two cases. This regimen proved active in advanced breast cancer following anthracycline-containing chemotherapy, and the 3-day schedule could be offered to such patients with acceptable toxicity.

A phase II study of interferon alpha and low-dose subcutaneous interleukin-2 in advanced renal cell carcinoma.

The activity of the drugs employed in the treatment of metastatic renal cell carcinoma, including biological response modifiers, is limited; one of the aims of clinical research in this area is to maintain the benefits of treatment whilst reducing its toxicity to a minimum level. We have evaluated toxicity and response of the combined administration of recombinant interferon alpha (IFN alpha) and low-dose subcutaneous (s.c.) recombinant interleukin-2 (IL-2) in patients with advanced renal cell carcinoma. A group of 20 previously untreated patients with advanced renal cell carcinoma were included in the study. Treatment consisted of 3 MU/m2 recombinant IFN alpha daily i.m. continuously, and 0.5 MU/m2 recombinant IL-2 twice a day s.c. on days 1-5 for the first week, followed by 1 MU/m2 twice a day for 5 days in the following weeks. For IL-2, a 1-week rest was allowed after 4 weeks of treatment. Response was assessed after 3 months of therapy. Three objective responses were seen, one complete and two partial. Eight patients had stable disease. The median time to progression was 6 months; the median survival for all patients was 14 months. Side-effects were low, limited to grades 1 and 2 in the majority of patients, and included fever, anemia, leukopenia, dyspnea, and abnormalities of liver and renal function tests. Any flu-like syndrome was judged moderate in most patients; however, one-third of the patients refused treatment mostly because of the flu-like syndrome. One of these was the patient experiencing a complete response, who virtually received IFN alpha alone. This regimen, similar to others employed in the treatment of advanced renal cell carcinoma, produced a 15% response rate (95% confidence interval, 0-31%) with 14 months median survival, moderate toxicity and low cost, and required no hospitalization. These data seem to indicate an effectiveness comparable to, and a toxicity lower than, that of regimens employing higher doses of IL-2.

Sucralfate prophylaxis of fluorouracil-induced stomatitis.

AIMS AND BACKGROUND: Various attempts have been made to prevent 5-fluorouracil-induced stomatitis, with unsatisfactory results. Sucralfate is an aluminum hydroxide complex of sulfated sucrose commonly used in the treatment of gastroduodenal ulcers. We used the compound in a phase II study to reduce and minimize the stomatotoxicity of 5-fluorouracil chemotherapy administered in a multiple-day schedule. METHODS: Fifty-two patients entered the study, and 129 cycles of chemotherapy were evaluated. Seven patients refused sucralfate rinses for taste intolerance. RESULTS: A low level of stomatotoxicity was recorded: grade 2 stomatitis was observed after 14 cycles (10.8%) and grade 3 after 3 cycles (2.3%). CONCLUSIONS: Sucralfate administration could have a role in the prevention of 5-fluorouracil-induced stomatitis.

Granisetron plus dexamethasone in moderately emetogenic chemotherapy: evaluation of activity during three consecutive courses of chemotherapy.

In this study we evaluated the antiemetic activity of a combination of 3 mg granisetron in a short i.v. infusion followed by 12 mg dexamethasone i.v. in 64 patients with cancer receiving moderately emetogenic chemotherapy scheduled in a single day. No patient had previously undergone chemotherapy and three consecutive cycles were evaluated. Response to antiemetic treatment was graded as follows: complete response, no episodes of vomiting; major response, only one episode; minor response, two to four episodes; failure, more than four episodes. Nausea was graded as absent, mild, moderate or severe (patients bedridden). At the first cycle a complete protection from acute vomiting and nausea was achieved in 95% and 73% of patients respectively; the rate of complete response for delayed vomiting was 90%, while 45% of patients complained of delayed nausea. The antiemetic and antinausea efficacy remained substantially unchanged during the second and third cycles of chemotherapy. Constipation and headache were the most frequent adverse events. In conclusion this antiemetic regimen appears very effective in preventing nausea and vomiting in moderately emetogenic chemotherapy.