Liver function tests and lidocaine metabolism (MEGX test) during i.v. CMF therapy in breast cancer.

The measurement of monoethylglycinexylidide (MEGX test) is considered a sensitive method for the evaluation of hepatic metabolic capacity. The multidrug chemotherapy CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/ m2, 5-fluorouracil 600 mg/m2) is widely used in breast cancer patients but very few clinical studies have investigated its possible liver toxicity. We have prospectively evaluated the possible acute liver toxicity after a cycle (i.e. two courses) of CMF by means of the measurement of standard liver function tests and of MEGX, i.e. the main lidocaine (Lid) metabolite after the i.v. injection of Lid. Consecutive patients (n = 15), aged 43-68 years, were radically operated on because of M0 primary breast cancer and candidates for adjuvant CMF because of nodal axillary involvement (pN1) were studied. Tests were performed before the first (given at day 1) and 48 h after the second course (given at day 8) of an i.v. CMF regimen to be repeated every 28 days. Full blood count, serum ALT, AST, gamma-GT, alkaline phosphatase and albumin were measured with standard methods. To investigate the appearance of MEGX, blood samples were taken before, and 5, 10, 15, 20, 25, 30 and 60 min after i.v. Lid injection. MEGX serum concentration was measured by means of a fluorescent polarization immunoassay. We found no significant variation between pre- and post-CMF standard liver function tests with the exception of ALT levels, which, however, decreased (mean 48%, p < 0.05). The MEGX serum concentration was significantly increased over the sampling time period and the 42% mean rise was statistically significant (p < 0.001). Moreover, the post-CMF increase of circulating MEGX was steeper than the basal pre-CMF values. The slopes relating to the curves of MEGX formation over the first 20 min were 3.30 and 2.24, respectively (p < 0.001). In conclusion, no hepatic acute toxicity was observed during the CMF chemotherapy. Further studies are required to understand the meaning of the unexpected MEGX rise.

Effectiveness and toxicity of "BELD" polychemotherapy in advanced malignant melanoma.

From January 1985 to December 1987, 17 patients with advanced malignant melanoma were treated with the polychemotherapy regimen BELD (bleomycin, 15 mg subcutaneously on day 1 and 4, vindesine 3 mg/m2 intravenously on day 1 and 5, CCNU 80 mg/m2 orally on day 1 and DTIC 200 mg/m2 intravenously on day 1 through 5) proposed as effective (CR + PR 45%) and tolerable. All patients were evaluable for toxicity and 14/17 also for response after 2 BELD cycles (total n. of cycles was 54). Criteria for response were just the same as those used by Young et al. A complete remission and a partial remission (2/14) have been observed at lymph nodal level, the unique sites of the disease in these two patients. Remission lasted 6 and 4 months, respectively. Two other patients showed a minimal response of 2 and 3 months duration (lymphonodal and cutis, respectively); 9 patients had stabilized disease of 5 months median duration. One case of progression of disease was observed. However, toxicity was relevant because of 2 early deaths after the first cycle, most probably therapy related, nausea and vomiting (82%), leukopenia (17%) and muscle rigors (11%).

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.

[Cyclophosphamide, adriamycin and platinum (CAP) in the preoperative neoadjuvant phase and the therapy phase]. / Ciclofosfamide, adriamicina e platino (CAP) in fase neoadiuvante preoperatoria e in fase curativa.

Forty-two patients with metastasized, and 7 patients with locally advanced forms of carcinoma of the breast were treated with a combination of three drugs: CTX 200-400 mg/sq.m. on days 1, 3 and 5, ADM 40 mg/sq.m. on day 1, and DDP 30 mg/sq.m. on days 1, 3 and 5 (CAP), every 21 days. The 42 patients with metastasized carcinoma had already received substantial pre-treatment by surgery and with adjuvant polychemotherapy +/- chemotherapy on recurrence +/- hormonotherapy +/- radiotherapy. The disease sites were: bone (30%), skin (19%), lymph nodes (13.5%), pleura (12.5%), lung (12%) and liver (11%). The 7 patients with locally advanced carcinoma had not been pre-treated; they received the same chemotherapy in the pre-operative neo-adjuvant phase. Positive responses to CAP in the cases with metastasized carcinoma according to individual disease sites (37 pre-treated patients assessable after at least two courses of therapy) were as follows in percentage terms: 24% bone lesions, 56% skin lesions, 77% lymph node lesions, 30% liver lesions, 56% lung lesions, 22% pleural lesions. 3/37 patients (8%) showed complete remission in all disease sites, while 6/37 showed partial remission. This percentage (8 + 16 = 24%) is encouraging, as CAP, in these patients, represents on average the 3rd to 4th line of therapy. Responses to neo-adjuvant CAP therapy (7 patients assessable after at least two courses of therapy) were as follows: 5 patients showed partial remission after 3-6 courses, 1 complete remission, and 1 objective improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

[Bone scintigraphy in mastectomized patients with and without chemotherapy]. / La scintigrafia ossea in pazienti mastectomizzate, sottoposte o no a chemioterapia.

Follow'ups were conducted on 130 mastectomized patients, periodically subjected to bone scintigraphy in addition to conventional tests. 89 of the patients had received chemotherapy and 41 had not. The results obtained show the value of scintigraphy for both accurate staging and follow-up in such patients.