From January 1991 to August 1993,237 women with metastatic breast cancer were recruited into a multicentric phase II clinical trial designed to assess the cardioprotective activity of Cardioxane (ICRF-187). All patients were treated with 5-fluorouracil 500 mg/m², doxorubicin 50 mg/m², cyclophosphamide 500 mg/m² (FDC) and Cardioxane 1000 mg/m², in cycles repeated every 3–4 weeks. Cardiac functions were assessed at baseline by physical examination, ECG, and resting ultrasound left ventricle ejection fraction (LVEF). The same tests were repeated regularly after the 3rd, 6th, 8th cycle and every additional 100 mg/m² of doxorubicin. At the end of the study there were 212 evaluable patients. Prior to analysis, patients were stratified according to the presence of cardiac risks at study entry. One hundred thirty-three patients (63%) bore one or more cardiac risks. The average total cumulative dose of doxorubicin administered to the group was 311 mg/m² (range: 200–900 mg/m²). Overall response (CR + PR) was 49.5% (105/212), with 12% of patients entering complete remission. General toxicity (WHO grading) was mild and tolerable; no excessive myelosuppression or related symptoms were observed. Three patients from the risk group experienced cardiotoxity, with an LVEF fall below 45%, and had to be removed from the study. Another 3 patients (1 from the risk group) were removed from the study due to clinically documented congestive heart failure after 200, 300 and 400 mg/m2 of doxorubicin. In our study, Cardioxane (ICRF-187) did not influence the antitumor efficacy of FDC chemotherapy, nor did concomitant administration of Cardioxane and chemotherapy result in any other or severer toxicity than that already known for this regimen. Finally, the observation that 51 % of patients with preexisting cardiac risks received doxorubicin at dose range of 450–900 mg/m² without significant clinical or laboratory signs of cardiotoxicity supports the evidence that Cardioxane provided cardiac protection offering the possibility of longer doxorubicin chemotherapy.

Serum levels of AFP, CEA, hCG, hPL and SP₁ were measured by specific radioimmunoassays in 111 patients with testicular germ cell tumors. Seminomas, mature teratomas and ‘pure type’ embryonal carcinomas, as well as the latter two types of tumor with seminomatous admixture, do not produce markers unless in advanced stages when they may do so (small amounts of hCG, hPL and SP₁). Tumors composed of yolk-sac elements alone or mixed with embryonal carcinoma produce AFP; of syncytiotrophoblastic elements – hCG, hPL or SP₁; and teratomas with differentiated structures- CEA. Compound tumors can produce any of the five markers. When present in serum after orchiectomy or lymphadenectomy, the markers are useful both in diagnosis of the tumor elements that metastasized and in staging; whereas their absence does not exclude regional or distant metastases which may contain only marker-negative elements, e.g., due to changes in tumor histology. Measurement of the serum levels of the markers informs about the remaining regional tumor elements or latent metastases and therefore is more useful than immunoperoxidase staining which provides information on the already dissected structures only.

61 patients with seminoma and 113 with nonseminomatous germ cell tumors of the testis were treated according to the histology, stage of disease, and serum levels of tumor markers (CEA, AFP, hCG, hPL and SP₁). 33 were stage I, 63 stage II, and 78 stage III patients. Most patients with seminoma, mature teratoma, immature teratoma, and ‘pure type’ embryonal carcinoma, as well as the latter three types with seminomatous admixture, had normal serum levels of the markers. Sometimes, slightly elevated levels of hCG suggested the presence of metastases. But, serial measurements of the markers were seldom useful in monitoring therapy. The 5-year tumor-free survival rates were favorable: 100% for stage I and II disease; and 57 or 44% for, respectively, stage III seminoma or the other tumors amounting to 10% of the nonseminomatous group. The role of the five markers was significant in patients with teratoma with malignant transformation, choriocarcinoma, endodermal sinus tumor (EST), and embryonal carcinoma or teratocarcinoma with an admixture of EST or choriocarcinoma or both. Elevation of a marker was a grave prognostic sign. The 5-year survival rates were 100, 16, and 4% for stages I, II and III disease, respectively. An elevated level of one or more of the markers assayed was always useful for monitoring therapy. Decreasing level indicated regression. However, return of an elevated level to normal did not indicate eradication of all tumor and called for diagnosis by imaging modalities. Constantly elevated or increasing marker levels during treatment indicated resistance to therapy. An increasing level from any nadir during remission indicated recurrence. Elevated levels of any of the five markers tested were as important as imaging modalities, and often more sensitive.

No abstract

The therapeutic efficacy of the combination of epirubicin + dibromodulcitol was evaluated in 108 previously treated or untreated patients with advanced breast cancer. The overall response rate was 39.8%, complete remission 3.7% (mean duration 6.3 months) and partial remission 36.1 % (mean duration 3.5 months). The response was rated in function of age, menopausal status, performance status and previous therapy. Toxicity (in case of 115 patients) was evaluated according to the WHO recommendation. The similar therapeutic effectiveness and less toxicity of the above drug combination compared to ADM + DBD regimen are demonstrated.