A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide, and cisplatin followed by radiotherapy versus radiotherapy alone in patients with localized uterine sarcomas (SARCGYN study). A study of the French Sarcoma Group.

BACKGROUND: There is no proven benefit of adjuvant treatment of uterine sarcoma (US). SARCGYN phase III study compared adjuvant polychemotherapy followed by pelvic radiotherapy (RT) (arm A) versus RT alone (arm B) conducted to detect an increase ≥ 20% of 3-year PFS. METHODS: Patients with FIGO stage ≤ III US, physiological age ≤ 65 years; chemotherapy: four cycles of doxorubicin 50 mg/m² d1, ifosfamide 3 g/m²/day d1-2, cisplatin 75 mg/m² d3, (API) + G-CSF q 3 weeks. Study was stopped because of lack of recruitment. RESULTS: Eighty-one patients were included: 39 in arm A and 42 in arm B; 52 stage I, 16 stage II, 13 stage III; 53 leiomyosarcomas, 9 undifferenciated sarcomas, 19 carcinosarcomas. Gr 3-4 toxicity during API (/37 patients): thrombopenia (76%), febrile neutropenia (22%) with two toxic deaths; renal gr 3 (1 patient). After a median follow-up of 4.3 years, 41/81 patients recurred, 15 in arm A, 26 in arm B. The 3 years DFS is 55% in arm A, 41% in arm B (P = 0.048). The 3-year overall survival (OS) is 81% in arm A and 69% in arm B (P = 0.41). CONCLUSION: API adjuvant CT statistically increases the 3 year-DFS of patients with US.

Verapamil increases the survival of patients with anthracycline-resistant metastatic breast carcinoma.

BACKGROUND: Verapamil (VER), a potent calcium channel blocker, has been found to overcome P-gp-mediated multi-drug resistance (MDR) and to increase sensitivity to cytotoxic anticancer drugs in refractory myeloma and non-Hodgkin lymphoma. The value of VER for treating solid tumors is still a matter for debate. PATIENTS AND METHODS: We performed a prospective study in 99 patients with anthracycline-resistant metastatic breast carcinoma (MBC), to assess the clinical effect of oral VER given in association with chemotherapy. Instead of retreating patients with anthracycline, we used a partially noncross-resistant regimen (VF), combining vindesine (VDS) and 5-fluorouracil given as a continuous infusion (5-FU CI). Patients were randomly assigned to two cohorts. One cohort (47 patients) was treated in 28-day cycles, each involving the administration of VDS (3 mg/m2 i.v. bolus on days 1 and 10) and 5-FU CI, (400 mg/m2/day i.v. from day 1 to day 10). The other cohort (52 patients) received the same VDS and 5-FU treatment and an additional oral VER treatment (240 mg/day divided in 2 doses), from day 1 to day 28 of each cycle. Patients were treated until progression. RESULTS: The treatment was well tolerated and no side effects that could be attributed to VER were detected. Patients treated with VER had longer overall survival (OS) (median OS: 323 vs. 209 days, P = 0.036) and a higher response rate (27% vs. 11%, P = 0.04) than those not given VER. Progression-free survival (PFS) was also longer but the difference was not statistically significant (median PFS: 4.6 and 2.7 months for the VER and non-VER groups respectively, P = 0.6). CONCLUSIONS: This clinical trial demonstrates that a chemosensitizer, such as VER, can increase the survival of MBC patients with acquired anthracycline resistance.

[Cancer of the breast at the time of diagnosis. A national CANAM study: analysis of 3007 cases]. / Le cancer du sein au moment du diagnostic. Etude nationale de la CANAM: analyse de 3,007 cas.

Between April 1988 and February 1990, 3,007 cases of female breast cancer were recorded among people insured by CANAM*; 118 cancers were bilateral from the start and 2,889 were unilateral. At the time of diagnosis the patients' age ranged from 24 to 101 years (median: 60 years), and 35.6 percent of the tumours were virtually subclinical. Lymph node involvement was clinically absent in 75 percent of the cases and histologically absent in 57 percent. In women under 50 the proportion of small TO-T1 tumours was greater than 40 percent, which pleaded for detection before the age of 50 years. Conversely, in economically weak populations and in women who were followed up for cancerous disease, breast cancer was diagnosed at a later stage. In older (retired) women (median age: 74), who accounted for 44 percent of the whole population, the proportion of advanced tumours was practically doubled (T4: 11 percent versus 6 percent), and the probability of metastases at the time of diagnosis had risen from 4.2 to 6.1 percent. In these patients, clinical examination once a year should contribute to an earlier diagnosis.