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.

Preoperative staging of primary breast cancer. A multicentric study.

This article reports on a consecutive series of 3627 breast cancer (BC) patients undergoing preoperative staging by chest x-ray (CXR), bone x-ray (BXR) or bone scintigraphy (BS), and liver ecography (LE) or liver scintigraphy (LS). The detection rate (DR) of preclinical asymptomatic distant metastases depended on the T and N category (TNM classification system), and was very low (CXR: 0.30%, BXR: 0.64%, BS: 0.90%, LE: 0.24%, LS: 0.23%). The sensitivity, determined after a 6-month follow-up, was below 0.50% for all tests. The highest value (0.48%) was recorded for BS, which also had the lowest specificity (0.95%). The entire preoperative staging policy using the studied tests seems questionable due to poor sensitivity and an extremely low DR of distant metastases.

Acquired factor VIII inhibitor in a non-haemophilic patient: successful treatment with plasma exchange associated with factor VIII concentrate and immunosuppressors.

We report the successful treatment of a 55-year-old man with an acquired factor VIII inhibitor, the appearance of which followed surgery for a carcinoma of the biliary tract. The patient, who had recurrent life-threatening bleeding episodes, was treated with intensive plasmapheresis, factor VIII concentrates, azathioprine and methylprednisolone. Disappearance of the inhibitor was observed after the second series of plasma exchanges. Controls 2 and 3 months after treatment confirmed the complete absence of the inhibitor and normal levels of factor VIII. The crucial role of plasma exchange is considered and discussed.