A two-step reevaluation of high-dose amsacrine for advanced carcinoma of the upper aerodigestive tract: a pilot phase II study.

Results of amsacrine studies in different solid tumors with a dose of 85 mg/m2/24 h x 1 quo 3 weeks have been, in general, disappointing. Although only a few patients with head and neck cancer have been included in broad phase II studies, several responses have been reported, but detailed data concerning responders are lacking. In the present study, amsacrine (Amsidil, Godecke-Parke Davis) was administered at an increased dose of 85 mg/m2/24 h x 3 (total dose per cycle 255 mg/m2) quo 3-4 weeks. 25 patients with advanced carcinoma of meso and hypopharynx were included in the first step of this phase II study (11/25 with histological grades I/II and 14/25 with histological grades III/IV; 10/25 pretreated with radical radiotherapy and 15/25 previously untreated), and 5 patients with undifferentiated carcinoma of the nasopharyngeal type (UCNT), all previously treated. 5/30 patients achieved a complete response (CR) and 5/30 a partial response (PR), the overall response rate being 10/30. Regarding the histology grade, only 1/11 patients with grade I/II carcinoma of meso and hypopharynx achieved a PR with no CR, but 5/14 with grade III/IV from the same group achieved a CR. Out of 10 pretreated patients only one achieved any response and none of the 5 patients with UCNT. Thus, in the second step of this study, high dose amsacrine was evaluated in the target group of previously untreated patients with advanced grade III/IV carcinoma of meso and hypopharynx. 20 patients were included in the second step and all were evaluable for activity. A CR was achieved for 6/20 patients and a PR for 7/20 patients (response rate 65%, 95% confidence interval 44%-86%). Hematological toxicity from both steps included grade IV granulocytopenia in 25/50 patients (50%, 95% confidence interval 36%-64%) and grade IV thrombocytopenia in 18/50 patients (36%, 95% confidence interval 23%-49%). High dose amsacrine seems to be a toxic, but very effective drug as first-line treatment for poorly differentiated carcinoma of meso and hypopharynx, and further studies seem warranted.

Randomised study of high-dose epirubicin versus high-dose epirubicin-cisplatin chemotherapy for advanced soft tissue sarcoma.

A randomised study was started in chemotherapy-naive patients with advanced soft tissue sarcomas who received either epirubicin 60 mg/m2/24 h (total dose for cycle 180 mg/m2) days 1, 2 and 3, (group A) or epirubicin 60 mg/m2/24 h days 1, 2 and 3 and cisplatin 30 mg/m2/24 h days 2, 3, 4 and 5 (group B). The maximal number of cycles foreseen in both groups was eight. Cardiotoxicity of the regimens was monitored by serial LVEF determinations. 106 patients entered this study, 50 (45 evaluable for activity) randomised to group A, and 56 (54 evaluable for activity) to group B. The groups were well balanced for age, sex, performance status and histological type. In group A, there was 1 complete response (CR) and 12 partial responses (PR), the overall response being 13/45 (29%); in group B, there were 7 CRs and 22 PRs, the overall response being 29/54 (54%). The difference between the overall response was statistically significant (chi 2 = 6.19, P < 0.025). The epirubicin-cisplatin regimen was found to be more toxic for platelets and more emetogenic, but cardiotoxicity, either acute or cumulative, was not found to be a major problem in both groups. However, a complete responder receiving a cumulative epirubicin dose of 1440 mg/m2 died from congestive heart failure after a disease-free interval of 27 months. The high response in group B could be the result of the synergism between high-dose epirubicin and cisplatin in patients with advanced soft tissue sarcomas.

Richter syndrome with emphasis on large-cell non-Hodgkin lymphoma in previously unrecognized subclinical chronic lymphocytic leukemia.

The authors report seven cases of Richter's syndrome, i.e. of large-cell non-Hodgkin's lymphoma (NHL) arising in association with chronic lymphocytic leukemia (CLL). Six patients had the recently recognized variant of this syndrome, occurring in patients with previously undiagnosed subclinical CLL. All patients were treated with aggressive chemotherapy and a complete response of large cell NHL was achieved in 4/7. A complete response of NHL was observed in 3 out of 6, and a partial response in 2/6 patients with simultaneous occurrence of subclinical CLL and large cell NHL (response rate 5/6). Our findings might suggest that patients with Richter syndrome occurring in previously undiagnosed subclinical CLL could represent a better prognostic group in the overall population of patients with large cell NHL transformation of CLL.

[A pilot study of high-dose zorubicin in advanced stages of soft tissue sarcoma in adults]. / Etude pilote de la zorubicine à hautes doses dans les stades avancés des sarcomes des tissus mous de l'adulte.

High-dose anthracyclines, doxorubicin 75 mg/m2 and epirubicin 150-180 mg/m2, are the most active drugs in the treatment of advanced soft tissue sarcoma. These dosages are associated with significant hematological toxicity for both drugs and a high risk of cardiotoxicity for doxorubicin. The aim of this pilot study was to investigate the activity of zorubicin in advanced soft tissue sarcoma, with a dosage supposed to be equihematotoxic to epirubicin 180 mg/m2. Twenty of 21 patients who had been included in the study were evaluable for response, 15 males and five females, median age 41 (range 20-67) years. All patients received zorubicin 600 mg/m2 per cycle divided in 3 days, the intercycle interval being 4 weeks. The cardiac function was monitored by determinations of left ventricular ejection fraction before each cycle. Therapeutic response was the following: 2/20 patients (10%) complete response, 6/20 (30%) partial response, 6/20 (30%) stable disease and 6/20 (30%) progressive disease, the overall response rate being 8/20 (40%). Complete responses were observed in a patient with undifferentiated sarcoma of the mediastinum and in a patient with unresectable angiosarcoma of subcutaneous tissues. The major toxicity was hematological, with granulocytopenia grade 4 occurring in 42/66 cycles, and the nadir on day 10 of the treatment cycle. Nine of 66 cycles were complicated by febrile neutropenia and stomatitis of any grade was recorded in only 1/66 cycles. No cumulative cardiotoxicity was observed up to a total cumulative zorubicin dose of 3,000 mg/m2.

[Influence of steroid receptors content in primary breast cancer on early relapse pattern]. / Uticaj sadrzaja steroidnih receptora u primarnom karcinomu dojke na prirodu ranog recidiva bolesti.

The early relapse pattern was followed in 165 operable breast cancer pts: 81 pts in stage I of the disease being without any adjuvant treatment, and 84 pts in stage II receiving systemic adjuvant chemo-, hormono-, or chemohormonal treatment, according to nodal status, histological grade of tumours and positivity of progesterone receptors (PR > 20 fmol/mg), as the functional parameter of primary tumour hormonodependency. The analyses of early relapses, occurring within the first 24 months, were based on quantitative oestrogen and progesterone receptor values, known as the prognostic and predictive factors for the early relapse pattern, and for the responce to adjuvant treatment. In stage I pts ER distribution showed lower values in pts with relapse, as compared to the group without relapse (0-115 vs. 0-464), and a tendency for relapse occurrence below the ER levels of 33 fmol/mg. Such a trend was not found for PR. In stage II pts a remarkable trend towards lower values of both receptors was observed in relapsed pts. A trend towards lower receptor values existed in both stages in pts with visceral metastases (ER = 0-50 fmol/mg, PR = 0-64 fmol/mg), while in those with bone metastases the receptor levels tended to be higher (ER = 0-1 15 fmol/mg, PR = 0-278 fmol/mg). Our results indicate the importance of steroid receptor status as a prognostic factor as well as its role in prediction of the localization of early relaps in operable breast cancer.

CEA and CA 15-3 in pleural effusion of advanced breast cancer patients: clinical relevance and diagnostic value.

Serum and pleural effusion fluid were tested for CEA concentration in 83 advanced breast cancer patients, in 43 of whom CA 15-3 was also determined. All pleural effusions were clinically malignant. The sensitivity of the CEA test for the presence of pleural metastases was closer to that of the CA 15-3 test in effusion (0.59 and 0.79, respectively) than the sensitivity of CEA compared to CA 15-3 in serum (0.43 vs. 0.79). The use of two markers combined with cytology increased the diagnostic rate from 48% (cytologically positive) to 88% (cytologically positive and/or with one or both markers increased in effusion). A high diagnostic rate in cytologically negative effusions (65%), and in effusions presented as the sole metastatic involvement (100%), points to the clinical value of these two markers. Our results show that markers produced by pleural metastases may be secreted either into the effusion fluid or into serum, or both. This finding, as well as some other observations, are discussed in the present paper.

Estrogen dependence of primary breast cancer--correlation with histologic type and grade.

The purpose of this study was to investigate whether histologic type and grade of primary breast cancer are related to the estrogen and progesterone receptors. Our results showed that histologic type influenced the estrogen dependence through histologic grade. There was no difference in the estrogen and progesterone receptor content, when corresponding grades of different histologic types and estrogen dependence were confirmed by quantitative non-parametric analysis. It showed a direct relationship between estrogen and progesterone receptor content in all the three histologic grades and further that histologic grade defines three different groups in regard to progesterone receptor content.

[Intracranial malignant melanoma in childhood]. / Intrakrainjumski maligni melanom decjeg doba.

Malignant melanoma is a very uncommon tumour in childhood. Over the period from 1978 to 1987 998 children were treated with radiotherapy for different malignant diseases. Only two children were treated for melanoma. The authors present a 12-year-old boy with malignant melanoma of the central nervous system which appeared in the left parieto-occipital region. All clinical, laboratory, radiological and other examinations could discover no other lesion except the CNS (primary or metastatic). The boy was operated on (partial extirpation) and radiotherapy was performed with 60Gy/30f. The boy completely recovered for a short time. He died 14 months after the onset of symptoms and 12 months after the beginning of the treatment. This clinical course suggests a rapid progression of primary brain melanoma.