Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

PURPOSE: The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. PATIENTS AND METHODS: Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. RESULTS: Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes were strongly correlated with disease-free survival and overall survival in univariate analyses. Additionally, in a proportional hazard regression model and in an accelerated failure time model, metastatic axillary lymph nodes significantly influenced both disease-free survival and overall survival, whereas pathological response of primary tumor did so on disease-free survival only. CONCLUSION: After neoadjuvant chemotherapy, pathological responses of both primary tumor and metastatic axillary lymph nodes had a marked prognostic significance and influenced outcome for patients with locally advanced breast carcinoma. Our results suggest that maximal tumor shrinkage and sterilization of potentially involved axillary nodes may represent a major goal of neoadjuvant chemotherapy. Further studies are warranted to clarify whether these results reflect the therapeutic effect or intrinsic biologic factors of the tumor.

Double modulation of 5-fluorouracil by methotrexate and high-dose L-leucovorin in advanced colorectal cancer.

A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and L-leucovorin (L-LV) in patients with advanced recurrent (inoperable) or metastatic colorectal carcinoma (ACC). Between July 1993 and October 1995, 41 patients with ACC received a regimen that consisted of MTX 150 mg/m2 i.v., infused over a 20-minute period at hour 0, followed 19 hours later by L-LV 250 mg/m2 in a 2-hour i.v. infusion. 5-FU, 900 mg/m2, was administered by i.v. push injection at hour 20. Beginning 24 hours after MTX administration, all patients received four doses of L-LV, 15 mg/m2 i.m., every 6 hours. Cycles were repeated every 15 days. Two patients were not assessable for response. Objective regression was observed in 11 of 39 (28%) patients, [95% confidence interval (CI), 14-42%]. One (2%) patient achieved complete response (CR) and 10 (26%) partial response (PR). No change was recorded in 15 (39%) patients and progressive disease was noted in 13 (33%) patients. The median time to treatment failure was 6 months and the median survival time was 10 months. Toxicity was within acceptable limits, but one therapy-related death due to severe leukopenia was observed. The dose-limiting toxicity was mucositis. Eight episodes of grade 3 or 4 stomatitis were observed, and were responsible for dosage modifications of MTX and 5-FU. In conclusion, further in experimental and clinical studies are clearly necessary in order to design the best modulatory strategy of 5-FU.

[Temporal electric stimulation and right ventricular extension in acute postero-inferior myocardial infarction. Influence on clinical characteristics and prognosis]. / Estimulación eléctrica temporal y extensión ventricular derecha en el infarto agudo de miocardio postero-inferior. Influencia sobre las características clínicas y el pronóstico.

In 386 patients with acute inferior myocardial infarction (AIMI) who were admitted to our institution from 1984 to 1990, temporary pacemaker (TP) was required in 34 patients (9%) due to disturbances in the genesis and/or conduction of the electric stimulus (Group I). The remainder, 352 AIMI, conform the Group II. Each group was divided into groups depending on the presence (Groups Ia and IIa) or absence (Groups Ib and IIb) of right ventricular necrosis (ECG criteria: ST elevation greater than 0.1 mV in a V3r and V4R). Clinical data (cardiovascular risk factors, history of myocardial infarction or angina, CPK and CK-MB peak, Killip class, atrioventricular block and right ventricular infarction) and hospital mortality rate and its cause were analyzed. The Group I patients related to Group II had significantly higher diabetes rate (p less than 0.01), CPK and CK-MB peak (p less than 0.001), Killip class (p less than 0.001), right ventricular involvement and atrioventricular block (p less than 0.001), the mortality rate equally was statistically higher (Group I, 11 patients, 31%, versus group II, 38 patients, 11%) (p less than 0.001). The Group Ia patients related to Group Ib had a higher CPK and CK-MB peak (p less than 0.001), Killip class and atrioventricular block (p less than 0.001). The mortality rate was statistically equal. The group IIb patients related to Group IIb patients had a higher CPK and CK-MB peak (p less than 0.001), without differences in the mortality rates.(ABSTRACT TRUNCATED AT 250 WORDS)