Cardiotoxicity of anthracycline in young breast cancer female patients: the possibility of detection of early cardiotoxicity by TDI.

Tissue Doppler imaging (TDI) was investigated for its applicability for detecting cardiac function and early cardiotoxicity in breast cancer patients treated with anthracyclines. A total of 40 women (age range 18 to 65 years) were enrolled, who had not received anthracyclines previously and had normal systolic and diastolic cardiac function. All healthy patients in the control group were of the same age. Each patient underwent not only standard echocardiographic measurements (ventricular dimensions and wall thickness, ejection fraction, E-wave deceleration time (DT), E/A ratio), but also specific imagings (E-septum separation, pulmonary venous flow), and in addition the myocardial velocity of many segments of mitral anulus obtained with pulsed wave tissue Doppler imaging were performed during the one year of observation period. Based on the results we found that systolic left ventricular function did not change significantly - neither in the study nor in the control group. Diastolic left ventricular function was impaired in 39 patients (97.5%), and 30 (75%) of these showed clear changes by means of both the traditional E/A ratio and TDI. Diastolic dysfunction in 9 patients (22.5%), however, could be detected only with TDI. The analysis of myocardial velocity in different segments showed that diastolic dysfunction does not develop in a homogeneous way but in a different way in segments. Diastolic function was intact in the control group during the study. The detectable myocardial damage occurred in the study group of young female patients without risk factors as a result of one year anthracycline therapy was so severe that the possible outcome might be serious congestive heart failure or death. Our results confirmed our assumptions that TDI is a more precise and useful examination method than traditional ones (E/A ratio or deceleration time) to demonstrate isolated diastolic dysfunction as a result of chemotherapy. Relevant extra information might be given by TDI compared to parameters describing diastolic functions depending on several changing values. TDI may become a regularly and more widely used noninvasive method to detect subclinical cardiotoxicity emerging after chemotherapy.

Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a randomized phase III multicenter trial.

PURPOSE: This phase III trial compared the efficacy and safety of doxorubicin and paclitaxel (AT) to 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line therapy for women with metastatic breast cancer. PATIENTS AND METHODS: A total of 267 women with metastatic breast cancer were randomized to receive either AT (doxorubicin 50 mg/m(2) followed 24 hours later by paclitaxel 220 mg/m(2)) or FAC (5-fluorouracil 500 mg/m(2), doxorubicin 50 mg/m(2), cyclophosphamide 500 mg/m(2)), each administered every 3 weeks for up to eight cycles. Patients had to have measurable disease and an Eastern Cooperative Oncology Group performance status of 0 to 2. Only one prior non-anthracycline, nontaxane-containing adjuvant chemotherapy regimen was allowed. RESULTS: Overall response rates for patients randomized to AT and FAC were 68% and 55%, respectively (P =.032). Median time to progression and overall survival were significantly longer for AT compared with FAC (time to progression 8.3 months v 6.2 months [P =.034]; overall survival 23.3 months v 18.3 months [P =.013]). Therapy was generally well-tolerated (median of eight cycles delivered in each arm). Grade 3 or 4 neutropenia was more common with AT than with FAC (89% v 65%; P <.001); however, the incidence of fever and infection was low. Grade 3 or 4 arthralgia and myalgia, peripheral neuropathy, and diarrhea were more common with AT, whereas nausea and vomiting were more common with FAC. The incidence of cardiotoxicity was low in both arms. CONCLUSION: AT conferred a significant advantage in response rate, time to progression, and overall survival compared with FAC. Treatment was well-tolerated with no unexpected toxicities.

[Chemoprevention of breast cancer - with special interest of tamoxifen] / Az emlôrák kemoprevenciója - különös tekintettel a tamoxifenre.

The adjuvant use of tamoxifen confers a survival advantage for patients with node-positive and node-negative breast cancer and demonstrated benefit when used alone or in combination with chemotherapy to treat advanced breast cancer.Tamoxifen prevents induced mammary cancer in rats, decreases the contralateral breast cancer incidence in humans, and its safety record in clinical practice is excellent. This finding led to the concept that the drug might play role in breast cancer prevention. In 1986 at the Royal Marsden Hospital a small pilot study was started, which would serve as a feasibility assessment for a larger trial to determine if tamoxifen prevents breast cancer. The trial shows no effect, because the study is too small for accurate results. Similarly, in another tamoxifen prevention study performed in Italy, the incidence of breast cancer did not differ between groups of tamoxifen and placebo. The negative finding of the study is readily explained by the relatively low risk of breast cancer development in the study population, the high drop-out rate and the small number of women who completed 5 years of treatment. In the NSABP P-1 prevention trial tamoxifen reduced the risk of invasive breast cancer by 49% and of noninvasive breast cancer by 50% in the increased risk population of 13.388 healthy women. The article summarizes the recent theoretical and practical data of the chemoprevention of breast cancer.

[Radiotherapy of benign disorders] / Jóindulatú betegségek sugárkezelése.

The radiation oncologist's primary concern is treatment of patients with malignant tumors but sometimes faces on occasion rare, non malignant disorders. The scarcity of disease incidence is reflected by the paucity of references for these diseases in the literature. This minimal exchange of information may make research and analysis difficult, tedious and not easily directed. Even with recognition of the risks of late skin injury, carcinogenesis, leukemogenesis and genetic damage from all ionizing radiation, radiation therapy also continues to be accepted treatment for benign diseases that do not respond to other methods of therapy. The purpose of this paper is to provide a short overview of the radiotherapy of most frequent benign disorders.

Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group.

PURPOSE: This phase III study compared docetaxel with mitomycin plus vinblastine (MV) in patients with metastatic breast cancer (MBC) progressing despite previous anthracycline-containing chemotherapy. PATIENTS AND METHODS: Patients (n=392) were randomized to receive either docetaxel 100 mg/m2 intravenously (i.v.) every 3 weeks (n=203) or mitomycin 12 mg/m2 i.v. every 6 weeks plus vinblastine 6 mg/m2 i.v. every 3 weeks (n=189), for a maximum of 10 3-week cycles. RESULTS: In an intention-to-treat analysis, docetaxel produced significantly higher response rates than MV overall (30.0% v 11.6%; P < .0001), as well as in patients with visceral involvement (30% v 11%), liver metastases (33% v 7%), or resistance to previous anthracycline agents (30% v 7%). Median time to progression (TTP) and overall survival were significantly longer with docetaxel than MV (19 v 1 weeks, P=.001, and 1 1.4 v 8.7 months, P=.0097, respectively). Neutropenia grade 3/4 was more frequent with docetaxel (93.1 % v62.5%; P < .05); thrombocytopenia grade 3/4 was more frequent with MV (12.0% v 4.1%; P < .05). Severe acute or chronic nonhematologic adverse events were infrequent in both groups. Withdrawal rates because of adverse events (MV, 10.1%; docetaxel, 13.8%) or toxic death (MV, 1.6%; docetaxel, 2.0%) were similar in both groups. Quality-of-life analysis was limited by a number of factors, but results were similar in both groups. CONCLUSION: Docetaxel is significantly superior to MV in terms of response, TTP, and survival. The safety profiles of both therapies are manageable and tolerable. Docetaxel represents a clear treatment option for patients with MBC progressing despite previous anthracycline-containing chemotherapy.

Multicentric extraabdominal desmoid tumour: a case report.

The very rare condition of multicentric desmoid tumours involving two distant and apparently independent sites is reported in a 17-year-old man. The tumours grew simultaneously and reached approximately equal size. No evidence of familiar polyposis or any other feature of Gardner's syndrome were noted. The proximal desmoid tumour developed from the left hip region and extended into the femoral bone, whereas the distal mass was attached to the left popliteal fossa infiltrating the flexor muscles, the nerves and vessels. On the basis of the good results published recently in the literature and our own earlier experiences, the intralesional resection of the desmoid tumours was completed with postoperative fractionated radiotherapy.

Combination of daily 4-h infusion of 5-fluorouracil and cisplatin in the treatment of advanced head and neck squamous-cell carcinoma: a South-East European Oncology Group study.

Between April 1986 and May 1989 a multicentre study was conducted to evaluate the efficacy of a 4-h intravenous infusion of 1000 mg/m2 5-fluorouracil (5-FU) followed by a 1-h infusion of 25 mg/m2 cisplatin (CDDP) given for 4 consecutive days every 4 weeks to patients with advanced squamous-cell carcinoma of the head and neck. A total of 189 consecutive patients entered the study, including 106 who had previously undergone chemotherapy and 83 who were chemotherapy-naive. Of the 165 evaluable patients, 96 (58%) responded to treatment, including 22 (13%) who achieved a complete remission (CR). In the group of previously untreated patients an objective response (CR+PR) was seen in 78% (CR, 14%) whereas in pretreated patients the response rate (CR+PR) was 40% (CR, 13%). The median survival period was 10 months. No significant difference in the duration of survival or of remission was found between the two groups in relation to previous therapy, tumour localisation, disease stage or performance status. Almost half of the patients (49%) experienced leucopenia but it was severe in only 11% of cases. Anemia (mainly WHO grades 1-2) occurred in 38% of the patients. Nausea and vomiting were common (84%). Nephrotoxicity (23%) was mild and of short duration. Moderate hair loss was seen in 42% of the patients, and phlebitis occurred in 8%. A few cases of cardiotoxicity and neurotoxicity were observed. This regimen is well tolerated and can be given even on an outpatient basis. The resultant response rate and side effects appear to be similar to those previously reported for combination chemotherapy with CDDP and continuous 5-FU infusion.

[Radiation moulage therapy of gingival tumors]. / Moulage-kezelés gingivatumornál.

An irradiation treatment technique, long ago known yet seldom employed, is reported on. With a patient, because of an inoperable gingiva-tumor, after percutan irradiation for complementary purpose radium-moulage treatment was employed. Due to the irradiation treatment the patient became symptomless.