Lonidamine significantly increases the activity of epirubicin in patients with advanced breast cancer: results from a multicenter prospective randomized trial.

PURPOSE: Some evidence in vitro and in vivo shows that lonidamine (LND) can positively modulate the activity of doxorubicin and epirubicin (EPI). On this basis, a multicenter prospective randomized trial was performed in patients with advanced breast cancer (BC) to determine if the addition of LND to EPI could increase the response rate of EPI alone. PATIENTS AND METHODS: From May 1991 to May 1993, 207 patients were enrolled onto this study and randomized to receive intravenous (IV) EPI (60 mg/m2 on days 1 and 2) alone or with LND (600 mg orally daily). EPI administration was repeated every 21 days until tumor progression or for a maximum of eight cycles. LND was administered continuously until chemotherapy withdrawal. RESULTS: Response rate was significantly superior for the EPI plus LND scheme compared with the single-agent EPI either considering assessable patients (60.0% v 39.8%; P < .01) or including all registered patients according to an intention-to-treat analysis (55.3% v 37.5%; P < .02). The distribution of the response rate according to the site of disease did not show any significant difference between the treatment arms, except for the patient subgroup with liver metastases in which the combination EPI plus LND resulted in a significant improvement of responses than EPI alone. Toxicity was moderate, and except for myalgia, no adjunctive side effects were observed in the EPI plus LND arm. Overall survival and time to progression were similar in both groups. CONCLUSION: This study confirms in vivo that the administration of EPI is enhanced by the concomitant LND administration.

Disease-free survival advantage of adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with node-negative, rapidly proliferating breast cancer: a randomized multicenter study.

PURPOSE: According to one of the most recent key scientific questions concerning the use of biomarkers in clinical trials, we investigated whether node-negative breast cancer patients, defined as high-risk cases on the basis of tumor cell proliferation, could benefit from cyclophosphamide, methotrexate, and fluorouracil (CMF) adjuvant therapy. PATIENTS AND METHODS: Two hundred eighty-one patients with negative nodes and rapidly proliferating tumors, defined according to thymidine labeling index (TLI), were randomized to receive six cycles of CMF or no further treatment after surgery +/- radiotherapy. RESULTS: The 5-year disease-free survival (DFS) was 83% for patients treated with CMF compared with 72% in the control group (P: =.028). Adjuvant treatment reduced both locoregional and distant metastases. When clinical outcome was analyzed in cell kinetic subgroups characterized according to tertile criteria, compared with patients in the control arm, 5-year DFS was significantly higher after adjuvant CMF in patients with TLI values in the second (78% v 88%, respectively; P: =.037) and third tertiles (58% v 78%, respectively; P: =.024). CONCLUSION: The results from this randomized clinical study indicate that patients with node-negative, rapidly proliferating tumors significantly benefit from adjuvant CMF.

Multicenter Phase II trial of intermediate dose cisplatin and vinorelbine in inoperable non-small cell lung cancer patients.

Vinorelbine (VNB) and cisplatin (CDDP) combination regimen was found active in the treatment of advanced non-small cell lung cancer (NSCLC) patients, but significant toxicity was observed. We evaluated the activity and toxicity of this combination administered at lower doses than previously reported. From March 1992 to March 1994, 99 patients (pts) were enrolled in a multicentric Phase II study and received intravenous CDDP at 80 mg/m2 on day 1, associated with intravenous VNB at 25 mg/m2 on days 1 and 8. Cycles were repeated every 3 weeks. The reduced doses led to a consistently lower myelotoxicity (8% Grade III-IV leukopenia) in comparison to two related Phase III studies, recently published. Conversely, the incidence of neurological toxicity was superimposable. Considering all eligible patients, the overall response rate was 28.3%, and this is similar to the results commonly observed employing the most active CDDP containing regimens. In conclusion, CDDP and VNB combination chemotherapy at the schedule performed in the present study led to a reduction of hematologic toxicity, while an appreciable activity was maintained.

Right ventricular metastasis from choriocarcinoma: report of a rare case and review of the literature.

A previously healthy gravida developed chest pain and progressive dyspnea several months after delivery. A right ventricular mass rising from the septum and floating through the pulmonary valve was detected, with multiple lung nodules. With the suspicion of a primary sarcoma of the heart, she was referred for cardiac surgery. Microscopic observation of the cardiac neoplasm revealed malignant trophoblast. There was no evidence of disease in the uterus and adnexa. Combination chemotherapy with EMA-CO schedule was instituted because of the high-risk score. A complete recovery was achieved after 20 weeks of treatment and the patient is free of disease 4 years after the end of chemotherapy and is now pregnant again.

Prognostic factors in metastatic breast cancer patients obtaining objective response or disease stabilization after first-line chemotherapy with epirubicin. Evidence for a positive effect of maintenance hormonal therapy on overall survival.

Randomized trials suggest that the outcome of metastatic breast cancer (BC) patients is not affected by the currently available therapies. Although response rates per se may be associated with survival prolongation, patients experiencing objective response may be those patients fated to have the longest natural disease history. The separation of responders from progressing patients after first-line chemotherapy could allow the selection of a more homogeneous subgroup in which further treatment strategies might achieve a better control of the disease. This study investigated the influence of some patient characteristics, disease characteristics, and previous treatments on the outcome of non progressing patients after first-line chemotherapy with epirubicin administration. We also evaluated the effect of the maintenance endocrine therapy in improving response rate and overall survival (OS). From May 91 to May 93, 207 patients were enrolled in a randomized trial aiming to compare the activity of epirubicin (120 mg/sqm) +/- lonidamine (600 mg/daily). Among the 169 patients attaining complete (CR), partial response (PR) or disease stabilization (SD), 65 were not randomly submitted to maintenance endocrine therapy (MET). Liver involvement, previous adjuvant chemotherapy and previous hormonal therapy (administered in adjuvant setting or for advanced disease) were found to negatively influence OS both in univariate and multivariate analysis. Differences in OS stratifying patients according to DFI, estrogen receptor status and PS did not attain statistical significance. Patients receiving MET survived significantly longer than those submitted to observation and this difference maintained the statistical significance also within patient subsets homogeneous for specific prognostic features. In conclusion, most prognostic factors for advanced BC have been confirmed in our series of patients obtaining CR, PR or SD to full dose epirubicin. The positive prognostic impact of MET is impressive and deserves confirmation in randomized studies.

[Osteoid osteoma of the femur neck (report of a case)]. / Osteoma osteoide del collo del femore (segnalazione di un caso)

After presentation of statistical data on the incidence of osteoid osteoma, a case of femoral neck localization is presented with details of medical history, clinical data, and X-Ray aspects. The operation itself is also described with anatomo-pathological and histological results. These data and the problems of differential diagnosis from other bone tumours is discussed.

Growth hormone and somatomedin behaviour in the newborn.

Human growth hormone (HGH) and somatomedin (Sm) concentrations have been studied in a group of newborns. Plasma HGH values were 41.17 +/- 24.26 (SD) ng/ml (14.00-90.00 ng/ml) and the Sm value was 0.59 +/- 0.43 (SD) U/ml (0.18-1.8 U/ml); the difference between these values and the ones observed in normal adults (2.45 +/- 2.53 (SD) ng/ml and 1.16 +/- 0.28 (SD) U/ml respectively) were statistically significant. While growth hormone values were higher than in normal adult controls, somatomedin was significantly decreased. It is possible that the dissociation between human growth hormone and somatomedin in newborn could reflect a reduced biosynthesis of the somatomedin-generating system and consequently a lack of a feed-back control on GH exerted by somatomedin.