Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial.

From February 1983 to January 1985, 497 patients with advanced breast cancer were randomly allocated to receive either epirubicin or doxorubicin in the following combination chemotherapy regimen: fluorouracil (5-FU) 500 mg/m2 intravenous (IV) on days 1 and 8; epirubicin or doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 500 mg/m2 IV on day 1 (FEC or FAC). Cycles were repeated every 21 days until progression or to cumulative doses of 700 mg/m2 for epirubicin and 550 mg/m2 for doxorubicin. Dose reductions were applied according to the standard criteria. Activity was evaluated in 443 patients (222 in the FEC arm and 221 in the FAC arm). The two experimental groups were comparable in age, performance status, menopausal status, histology, previous treatments, and site of the disease. The overall response rate (complete response and partial response [CR + PR]) was not significantly different: 53.6% for FEC and 56.5% for FAC. The median time to progression was 273 days for FEC and 314 days for FAC; the median survival time was 591 and 613 days, respectively. Leukopenia, anemia, nausea, and vomiting were significantly lower in patients treated with FEC. As for cardiotoxicity, four cases of congestive heart failure (CHF) were recorded among patients treated with FAC while only one was observed in the FEC group. These results indicate that epirubicin in a combination chemotherapy regimen is as active as doxorubicin and is significantly less toxic.

Factors causing dose variability in drug administration.

The variability of the drug dose actually given to cancer patients was analyzed. Three variability factors were quantitatively examined (body surface calculation, personalized dose calculation, and drug residuum in commercially available vials) and their variability was experimentally measured. A systematic reduction (mean, 7%; range, 2%-15%) and a random variability (4%-5%) of the dose given were demonstrated. These results draw attention to the role of some of the procedures of routine clinical activity in determining the amount of drug actually delivered. The analysis suggests that personalization of doses must be very accurate in both measurement and calculation and that the staff giving the drug needs to be carefully informed about the importance of drug residuum. The variability of the delivered dose can lead to the misclassification of patients in investigations on the dose-response relationship. This factor may be added to pitfalls previously reported to affect this type of retrospective analysis.

Aminoglutethimide in advanced breast cancer: plasma levels and clinical results after low and high doses.

Drug plasma levels, metabolism data and clinical results were evaluated after the daily administration of either 500 or 1,000 mg aminoglutethimide (AG, Orimeten, Ciba-Geigy) plus hydrocortisone acetate (20 mg b. i. d.). A total of 34 patients with advanced breast cancer entered the study: 17 were given 1,000 mg/day and 17 received 500 mg/day for at least 3 months. A novel HPLC method was developed to determine the levels of AG and its known metabolites [N-acetyl-AG (NAG), formyl-AG, nitroglutethimide, hydroxy-AG] in the biological samples. AG plasma concentration was significantly higher during the 1,000-mg/day regimen. NAG was the only metabolite observed in plasma, always occurring at concentrations lower than those of the parent drug. The ratios between NAG and AG levels distinguish two statistically different groups of patients. Irrespective of the dose, a partial response was observed in 44% of the patients; no change in 32% of cases; and progressive disease had an incidence of 24%. The probability of response was not dependent on the drug AUC or on the NAG/AG ratio and did not significantly depend on previous hormone treatment. Neither the plasmatic level of the AG or metabolite concentrations nor the NAG/AG ratio seemed to affect the incidence of side effects.

Phase II trial of mitomycin plus cisplatin in the treatment of advanced colorectal adenocarcinoma.

Cisplatinum may be synergistic if used in combination with other agents. This study was undertaken to investigate whether a mitomycin plus cisplatin in combination could show any promising data in colorectal cancer. The regimen did not show sufficient activity to encourage further trials.

Bleomycin, vincristine, mitomycin and cisplatin alternated with cyclophosphamide, 4'-epidoxorubicin and procarbazine in advanced non-small-cell lung cancer.

Thirty-eight patients with histologically confirmed non-small-cell lung cancer were treated with bleomycin, vincristine, mitomycin and cisplatin (BOMP) alternated with cyclophosphamide, 4'-epidoxorubicin and procarbazine (CEP). Twenty patients were randomized to start the treatment with BOMP and 18 with CEP. Patients underwent a median of 4 cycles (range, 1-8). The overall response rate was 36% with 2 clinical complete responses. The median duration of response was 6.5 months, the median survival time was 7.5 months, and 37% of patients survived for more than one year. The comparison between the two arms of this study and between this study and a previous investigation on the effectiveness of BOMP suggests that CEP regimen added to BOMP does not significantly improve patient outcome.

Survey on the use of questionable methods of cancer treatment. GOCS. Grupo Oncólogico Cooperativo del Sur República Argentina.

BACKGROUND: Despite the improvement of cancer treatments, unproven and useless therapies are widely adopted among cancer patients and their families. Little information is available on the actual magnitude of such a phenomenon. METHODS: Two anonymous, similarly aimed surveys were independently carried out in Italy and Argentina on cancer patients and their families by two research groups. RESULTS: Respectively 563 and 400 questionnaires were distributed. The percentage of patients and/or families involved in unsound care (17%) was similar in both surveys. Of these treatments, 20%-38% were proposed by physicians, but relatives, friends, and mass-media had an equally important role. The costs of such care was difficult to estimate. CONCLUSIONS: Real and exhaustive efforts are needed by Health Care Organizations, which must execute a policy of information and education towards the public and professionals, as well as declare unethical the use of unproven therapies which claim cancer cure but simply create false hopes. All oncologists should be aware of the use of these treatments for cancer patients, even concomitantly with conventional care.

4'epidoxorubicin plus verapamil in anthracycline--refractory cancer patients.

Four patients refractory to doxorubicin (DX) and 9 patients refractory to 4'epidoxorubicin (4'EpiDX) were treated with verapamil (VRP) (120 mg every 6 h for 3 days) plus 4'EpiDX (80 mg/m2 i.v. bolus, together with the 6th VRP administration). Three patients had partial remissions lasting 3, 3.5 and 7 months, respectively. Toxicity grading did not exceed usual levels. The study demonstrates that VRP, when added at conventional doses to 4'EpiDX, can induce objective responses in some patients refractory to anthracyclines.

Pilot study of intravenous administration of the acid-treated Salmonella minnesota R595 (Re) in cancer patients.

The clinical toxicity of acetic acid-treated "Salmonella minnesota" R595 (Re) organisms was evaluated in 24 cancer patients. Bacteria were injected i.v. four times at increasing doses for a total of 6.5 micrograms. This therapeutic regimen was free of major side effects (one patient had fever higher than 38 degrees C and 10 patients complained of pruritus). Furthermore, this bacterial preparation which possesses a more exposed lipid A on its surface, exhibited immunomodulating capacities in that it normalized the inverted T helper/T suppressor ratio and enhanced natural killer activity in tumor patients. The mechanisms of the lower toxicity and immunomodulating activities of these bacteria compared to other lipid A preparations are discussed.

Pharmacological data and technical feasibility of intraperitoneal 5-fluorouracil administration.

Via a surgically implanted Tenckhoff catheter, 5-fluorouracil was intraperitoneally administered to patients with malignant disease confined to abdominal space. Treatment was well tolerated without local complications. Peritoneal and plasmatic drug levels were measured, showing that: 1) peritoneal drug levels declined as a first order function; 2) plasmatic levels were very close to those reported for continuous i.v. administration, but peritoneal concentrations were much higher (log 1 to 3); 3) concentration x time product had a peritoneum: plasma ratio ranging from 120 to 1350. The hypothesized role of intraperitoneal 5-fluorouracil administration and the questions still to be answered are summarized.

Pharmacologic data and technical feasibility of intraperitoneal doxorubicin administration.

Seventy intraperitoneal administrations of doxorubicin were performed in 12 patients with malignant disease in the abdominopelvic space. Peritoneal and hematologic drug levels were measured by fluorimetric assay. A first-order decline in the peritoneal level was determined (T 1/2 96 +/- 18 min), with a mean drug absorption of 84% in 4 h (range 40-96%) and a mean ratio of a peak dialysate/peak serum level of 111 (range 12-390). Gastrointestinal toxicity was common and peritoneal phlogosis occurred twice. The doxorubicin level and the time of peritoneal exposure seem to be critical factors for major local toxicity. At a moderate concentration doxorubicin can be intraperitoneally administered, but its usefulness is probably confined to patients with minimal abdominal disease.

[Approach to the problem of economic costs of the medical therapy of tumors]. / Approccio al problema dei costi economici della terapia medica dei tumori.

The use of antitumoral drugs is increasing constantly. The economic cost pro capite of the commonest oncotherapeutic treatments has been analysed. The calculation is carried out on the basis of out-patient as well as in-patient treatment. The costs were identical in the hospital where the study was carried out due to the application of the recent regional health legislation. A number of considerations are made regarding the implications of unqualified use of the medical treatment of cancer.

Primary lymphoma of the vagina. A case report.

Primary vaginal non-Hodgkin lymphoma is really uncommon and may be misdiagnosed as inflammatory disease or solid cancer, so careful diagnostic procedures are needed, particularly as far as pathological and immunocytochemical evaluation is concerned. Most of these lymphomas present with follicular patterns and limited stage disease, so high cure rates are possible with surgery and/or radiotherapy, but chemotherapy has to be considered on the basis of clinical presentation and pathologic features. We report a case of vaginal lymphoma with primary bulky ulcered mass hat was treated with chemoradiotherapy.