Geroprotection in cancer prevention.

Clinical records from individuals followed for 5 years, 2000 to 2005, were reviewed. They were distributed in 3 cohorts of ages ranging from 51 to 60, 61 to 70, and 71 to 80 years, respectively. Each cohort included 2 groups of patients with diabetes type 2, one group treated with Metformin 850 mg/day, and the other one without pharmacological treatment. In all groups, for each individual, the mean variation of glycosylated hemoglobin, ferritin, lymphocyte count, total and subpopulations, was determined in blood using the measurement at the beginning and at the end of the 5-year follow-up. The number of all living individuals and cancer cases were also recorded in all groups at the end of the 5-year period. The results were consistent with the reported significance as biomarkers of aging of: the increase of glycosylated hemoglobin and ferritin, the decrease of the number of total lymphocytes and CD8+T, and the increase of T-Regulators. In this preliminary observation, the protection of Metformin on the variations of aging biomarkers was associated with survival and decline of malignancy incidence.

Clinical outcome and prognosis of patients with inflammatory breast cancer.

This report analyzes clinical factors affecting outcome in 26 patients with inflammatory breast cancer. Peau d'orange was the most common clinical finding at diagnosis (65%). A palpable breast mass (PBM) was noted in 65% with axillary lymph node involvement in 81% of patients. Eighteen patients were staged as stage IIIB and eight as stage IV. Initial metastases included supraclavicular nodes (five of eight), bones (one of eight), skin (one of eight), and liver (one of eight). All patients were treated with neoadjuvant chemotherapy (cyclophosphamide, doxorubicin, and fluorouracil, 18 patients; other, 8 patients). Partial response was the best clinical response attained in 38% of patients. Only one patient was treated with total mastectomy after neoadjuvant chemotherapy, and 19 patients received radiotherapy followed (2 patients) or not (17 patients) by mastectomy. The progression rate in stage IIIB patients was 78%, with distant sites of progression in 93% of patients and only 7% with local progression. Mean time-to-progression was 13 months (Kaplan-Meier estimates of 45% and 11% at 24 and 48 months, respectively). The median overall survival (OS) value of the entire population was 13.2 months (Kaplan-Meier estimates at 24 and 48 months of 21% and 12.5%). By Kaplan-Meier method and log-rank test, a better OS was correlated with stage IIIB (p = 0.002), a PBM at diagnosis (p = 0.01), and a favorable response to initial chemotherapy (p = 0.03). Our results confirm the better clinical outcome of patients with stage IIIB and PBM at diagnosis. They also support the role for combined treatment as the best modality approach for this disease. However, overall prognosis remained poor, with recurrence and death resulting from the disease.

Oral ftorafur plus intramuscular thiotepa as adjuvant chemotherapy in patients with breast cancer.

In this study, we evaluated the safety and efficacy of a combination of oral ftorafur administered together with intramuscular thiotepa as adjuvant chemotherapy for "early" breast cancer patients. A total of 30 patients with operated breast cancer were treated with 500 mg/m2 oral ftorafur for 10 consecutive days plus 20 mg/m2 intramuscular (im) administered thiotepa on d 1 and 8 every 28 d adjuvant chemotherapy. Eleven patients were premenopausal and 19 were postmenopausal, with a median age of 53 yr. The total number of cycles delivered was 259 (median: 10 cycles per patient). Toxicity was low and usually consisted of leukopenia WHO grade I-II (14%) and neutropenia grade I-II (6%). Gastrointestinal toxicity was minimal. The 5-yr disease-free survival and overall survival were 55% and 84%, respectively. Relapse occurred as bone metastases (50%), local recurrence (25%), and liver (17%) and brain (8%) metastases. Our preliminary data showed that oral ftorafur and im thiotepa is a well-tolerated regimen and could be a useful alternative to the intravenous parenteral route as adjuvant treatment for early breast cancer. Randomized trials are needed to assess the possible advantage of this regimen over intravenous schedules.

Heterogeneous distribution of tumor blood supply affects the response to chemotherapy in patients with head and neck cancer.

OBJECTIVE: To evaluate if the heterogeneous distribution of tumor blood supply affects the response to chemotherapy in patients with head and neck cancer. METHODS: We treated 25 stage III/IV patients with an intraarterial cisplatinum-bleomycin regimen. Prior to treatment, a blue dye was injected directly to tumors through the catheter. Well-stained areas were considered as profusely perfused areas whereas poorly stained areas were considered as poorly perfused areas. Biopsies of both areas of each tumor were taken prior to and after the treatment and the histopathological response was evaluated with the following grading: I, tumor disappearance; II, destruction of some tumor nests; III, no changes. RESULTS: Grade I responses were attained in 13/25 (52%) of profusely perfused areas against 1/25 (4%) of poorly perfused areas (p < 0.001). Moreover, there were significant differences (p < 0.001) in the overall responses: 21/25 (84%) in the profusely perfused areas versus 7/25 (28%) in the poorly perfused areas; and in grade III responses (4/25, 16% vs. 18/25, 72%). To determine a possible correlation between the histopathological responses obtained in profusely perfused and in poorly perfused areas of each tumor, we then calculated the Kendall's tau-b statistics, obtaining a tau value of 0.279 (p = 0.145). This data indicated that histopathological responses to chemotherapy of profusely perfused and poorly perfused areas were independent in each tumor. CONCLUSIONS: Heterogeneity in the distribution of tumor blood supply affects the response to chemotherapy by influencing the intratumoral delivery of therapeutic agents. After the administration of effective doses of anticancer drugs to a tumor, cells in profusely perfused areas receive enough to destroy them while cells in the poorly perfused areas are exposed to lower drug concentrations and, therefore, survive. This phenomenon could explain in part the difficulty in the treatment of human solid tumors.

Metastasis of bronchogenic carcinoma to the thumb.

Bone metastasis in the hand is rare. The etiology is quite different from that of metastasis to other bones; bronchogenic carcinoma is by far the most frequent case. Distal phalanges are mainly involved with irregular osteolysis and cortical destruction. Differential diagnosis of phalangeal metastasis includes osteomyelitis, rheumatoid arthritis and gout. The prognosis is always that of metastatic bronchial cancer with an average survival of three months. Treatment may involve distal digital amputation or antalgic radiotherapy. A case of bronchogenic carcinoma with metastasis to the thumb is presented. The metastasis was located in the distal phalanx of the left thumb. The primary tumor was located in the lung. Treatment consisted of amputation. The overall survival was five months.

Tratamiento del cáncer avanzado de la glándula mamaria con mitoxantrona, s-fluorouracilo y ciclofosfamida / Advanced breast cancer treatment with a combination of mitoxantrona, s-fluorouracil and ciclophosfamide

La combinación de mitoxantrona (M), 5-fluorouracilo (F) y ciclofosfamida (C), se administró como tratamiento inicial a 180 pacintes con cáncer avanzado de la glándula mamaria. Este estudio no comparativo se llevó a cabo en 7 diferentes instituciones médicas de Argentina, Brasil y México. Las dosis utilizadas fueron: mitoxantrona 12 mg/m2 i.v. día 1-21; 5-fluorouracilo 500 mg'm2 i.v. días 1-8-21 y ciclofosfamida 500 mg/m2 i.v. día 1-21. Las dosis se modificaron de acuerdo a la toxicidad presentada. En el 37% de los 1026 ciclos se presentó leucopenia <2000/mm3 y trombocitopenia <100,000/mm3 en el 16%. Náusea y vómito se presentaron en 82%, diarrea en el 27% y alopecia en el 74%. Respuesta global se observó en 88 de 147 pacientes valorables (60%); respuesta completa en 32 (21.8%) y respuesta parcial en 56 (38%), nos e observaron cambios en 38 (25.9%) y progresión en 21 (14.3%). La sobrevida promedio en este grupo fue de 25 meses; actualmente continúan con vida y sin evidencia de actividad tumoral, a más de 6 años, 24 (16.3%) de las pacientes. Aparte de la mielosupesión, en su mayoría neutropenia, la combinación MFC generalmente fue efectiva y bien tolerada con una baja incidencia de efectos secundarios. Se concluye que mitoxantrona en combinación con 5-fluorouracilo y ciclofosfamida, contribuyen a prolongar la sobrevida de las enfermas con cáncer mamario avanzado, mejorando la calidad de vida en un número importante de ellas. Se recomienda la combinación de MFC como esquema de priemra línea.

Intraarterial association of cis-platinum and bleomycin in head and neck cancer.

In order to establish the response and tolerance to the intraarterial association of cis-platinum and bleomycin, we have treated 38 patients with advanced head and neck cancer with the following dosages: continuous infusion of bleomycin, 20 mg/m2/day on days 1 and 2, and cis-platinum, 100 mg/m2 in a 3-hr infusion on day 3. Each treatment cycle was repeated every 21 days, the duration being conditioned to tolerance and response. All the patients underwent at least one complete series of treatment. The results were as follows: 11 patients (29%) had complete remission, and 22 (58%) had partial remission. No instances were ascertained of local toxicity (stomatitis, dermatitis). Except for 2 patients with reversible facial paralysis and 6 with anemia, no other signs of general toxicity were ascertained. In conclusion, the intraarterial combination of cis-platinum/bleomycin has proved highly effective (87% response) whereas the low index of local and general toxicity renders the drugs suitable for use before surgery and/or radiotherapy.