Treatment of refractory metastatic breast cancer with 5-fluorouracil and levofolinic acid as 48 hours continuous venous infusion.

Twenty-four consecutive patients with metastatic breast carcinoma (MBC) refractory to first line chemotherapy were treated with high-dose folinic acid (FA) 100 mg/m2 diluted in 250 cc of normal saline as 2 hour infusion followed by 5-fluorouracil (5FU) 400 mg/m2 bolus then 5FU 600 mg/m2 as continuous infusion for 22 hours. This therapy was repeated for 2 consecutive days. Chemotherapy was repeated every 15 days. All enrolled patients were evaluable for objective response. A complete response was achieved in 1 patient (4%) and a partial response in 6 cases (25%) for an overall response rate of 29% (confidence limits 18%-39%). The median duration of objective responses was 8.4+ months (range 3.0+/12.8). Six patients showed no change (25%) with a median duration of 4.0 months 11 patients progressed (46%). A subjective improvement in tumor-related symptoms was reported by all responding patients and in 3 patients with no change. Most patients (7/10) with symptomatic bone lesions had a subjective improvement with reduction in analgesic drugs consumption. Objective responses were observed at all sites of disease. In fact, responses were seen in the skin liver lung bore and rodal metastases. The median overall survival was 13.0+ months (range 4.0/16.2+). Over a total of 160 cycles (a mean of 6.6 cycles/patient) grade 1-2 leukopenia was seen in 9 patients (37%) grade 1 thrombocytopenia in 4 patients (17%) and grade 1 anemia in only 2 cases (8%). Grade 3-4 leukopenia or thrombocytopenia were not seen. Phlebitis at the injection vein occurred in 3/10 patients (30%) which refused to implant a central line. In patients with a central line or a port-a-cath no cases of vascular, toxicity were seen. Gastrointestinal toxicity was very mild with 9 patients (37%) suffering from grade 1-2 nausea/vomiting 6 patients (25%) complaining of grade 1-2 diarrhea and 6 patients with grade 1-2 stomatitis. Hand-foot syndrome was observed in only 1 patient. No cases of grade 3-4 gastrointestinal toxicities have been, observed. No cases of cardiotoxicity and/or neurotoxicity were recorded. The combination of high-dose FA and 5FU given as 48 hour continuous venous infusion every 2 weeks is active, at least in terms of objective response rate and tumor-related symptoms palliation against anthracycline-refractory MBC. These results compare favorably with bolus administration of FA and 5FU or other salvage regimens.

Treatment of refractory metastatic breast cancer with 5-fluorouracil plus levofolinic acid as continuous venous infusion: a phase II study.

Effective palliation of metastatic breast carcinoma (MBC) after the failure of front-line chemotherapy for advanced disease, often based on the use of anthracyclines and taxanes, is quite difficult to achieve due to the development of dominant neoplastic cellular clones highly resistant to further therapy. Therefore the therapeutic index of second and third line chemotherapeutic treatments is usually quite low. Thirty patients with MBC with progressive disease after anthracycline-based chemotherapy as first line therapy were treated with l-FA 100 mg/m2/day and 5FU 1000 mg/m2/day ad continuous venous infusion for 96 hours every 4 weeks. Most patients (60%) had multiple sites of disease at entry and had visceral lesions as the dominant site of disease. Twenty-eight patients were evaluated for objective response: two patients had clinically progressive disease before restaging after the third cycle of chemotherapy. These patients were considered progressive disease since all patients were included in an intent-to-treat analysis. Nine patients achieved partial response for an overall response rate of 30% (intent-to-treat analysis) with a median duration of 9.5+ months (range 4.0/14.0 months), and disease stability was obtained in 10 cases (33%) with a median duration of 5.5 months (5-11). Progressive disease was recorded in 9 patients. After a median follow-up of 11 months, the overall median survival time of the whole series of patients was 14.0+ months. Objective responses were recorded both at visceral and bone sites. Chemotherapeutic treatment was generally quite well tolerated. No toxic deaths were recorded. Among gastrointestinal side-effects grade 3 stomatitis was noted in 30% of patients, and grade 3 diarrhea in 10% of cases. Grade 3-4 leukopenia was observed in 23% of patients, but significant episodes of febrile neutropenia were limited (2 patients). Grade 3 thrombocytopenia was seen only occasionally in 1 patient. Grade 1 anemia was recorded in 10% of patients. Hand-foot syndrome was noted in 2 patients (7%). Cardiotoxicity was minimal. The combination of 5FU and high-dose I-FA given as 96 hour continuous venous infusion was active, at least in terms of the overall response rate, against anthracycline refractory metastatic breast carcinoma. These results compare favourably with bolus 5FU/FA or other salvage regimens in terms of antineoplastic activity, and is well tolerated both subjectively and objectively by most patients.

Therapeutic mammaplasties: full local control of breast cancer in one surgical stage with frozen section.

AIM: To evaluate the effectiveness of therapeutic mammoplasty with frozen section in achieving negative surgical margins in a single-stage surgery for breast cancer. METHODS: Fifty patients affected by early stage breast cancer treated by therapeutic mammaplasties were retrospectively reviewed in this study. Fifty-two therapeutic mammaplasties were accomplished. After resection the specimen was sent to pathologist for examination with frozen section. Tumour positive margins were defined as presence of cancerous cells at ≤ 2 mm from the edge of the specimen. In case of positive margins a second large re-excision was accomplished intra-operatively. All patients were followed every 4 months for the first 2 years and twice a year subsequently. RESULTS: Fifty-two procedures were evaluated (median follow-up of 72.6 months). The overall survival rate was 98% we had a single case of local recurrent disease (1.9%) that progressed to metastatic disease and patient's death. Frozen section as a diagnostic tool for identification of positive margins has been tested. In conclusion we report a sensitivity of 0.83 and a specificity of 0.93; the predictive positive value was 0.62 and the negative predictive value was 0.97, for a final accuracy of 0.94. CONCLUSION: Frozen section coupled to oncoplastic resections allows a proper control of local disease and can minimize any second surgical look for margins revision.

Disorder in organic charge-transfer single crystals: dipolar disorder in ClMePD-DMeDCNQI.

The unusual electronic, vibrational, and structural properties of the title compound are associated with the polar donor D=2-chloro-5-methyl-p-phenylenediamine, which is twofold disordered in single crystals. Its 3 D dipole generates random site energies with standard deviation sigma=0.35 eV that significantly alter the standard description of charge-transfer (CT) salts with nonpolar donors and acceptors. The average structure at 298 and 150 K is centrosymmetric, space group P1, and consistent with increasing degree of CT (or ionicity rho) on cooling. Vibrational spectra indicate that rho increases from approximately 0.3 at 400 K to approximately 0.6 at 80 K, with coincident Raman and infrared (IR) molecular modes in contrast with the centrosymmetric structure. Dipolar disorder is modeled by adding random site energies to Peierls-Hubbard models of CT salts, and sigma=0.35 eV is shown to suppress the Peierls instability for typical bandwidth and lattice stiffness, in agreement with the structural data. Disorder also breaks inversion symmetry and rationalizes coincident Raman and IR modes. The combination of site energies xp and the dipole operator P for systems with periodic boundary conditions leads at molecule p to (partial differentialP/ partial differentialxp)2 for the IR intensity polarized along the DA stack. The ensemble average of (partial differentialP/ partial differentialxp)2 for sigma=0.35 eV as a function of the ground-state ionicity rho accounts for the intensity variations of totally symmetric molecular modes of D and A, either on cooling at ambient pressure or on squeezing at ambient temperature.