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Background Schnitzler syndrome is a very rare, acquired, autoinflammatory disease of mostly adult onset with characteristic combination of chronic recurrent urticaria and monoclonal immunoglobulin M or G gammopathy predisposing the patients to malignant lymphoproliferation. In this work, we analyzed the results of bio-logical therapy with anakinra on a national level aiming to supply data for effective pharmaco-economic estimates, lay the grounds of nationwide patient registry, raise awareness among professional public and optimize provided health care. Patients and methods The retrospective study (10/ 2006- 9/ 2013) included six males with definite Schnitzler syndrome verified by the new Strasbourg criteria. All patients were pretreated with antihistamines, nonsteroidal antiinflammatory drugs and glucocorticoids. Four patients underwent two or more treatment lines including intravenous bisphosphonates, 2- chlorodeoxyadenosine (cladribine), interferonα, PUVA photochemotherapy, cyclosporine A, thalidomide, bortezomib, chlorambucil, cyclophosphamide, colchicine and methotrexate. Anakinra monotherapy was initiated in standard dosing (100 mg subcutaneously daily). Results Complete and partial remissions were achieved in five (83%) and one patients (17%), respectively. Complete remission was characterized by urticaria and pain regression (within hours), normalization of inflammatory markers (with--in days) and bone metabolism improvement assessed by the markers of osteoblastic osteoformation and osteoclastic osteoresorption in one case (within weeks). With normalized inflammatory markers (including interleukin6 and interleukin18), arthralgia and sporadic exacerbations of urticaria and fevers persist in the patient in partial remission with proven Q703K polymorphism in NLRP3 gene. The median treatment followup was 30.5 months (37.2 ± 31.2 (n = 6)). The dosing interval was prolonged in one case of complete remission to 48 hours. No serious adverse reactions occurred during anakinra application. Conclusion In Schnitzler syndrome, anakinra represents an effective, verified and safe medication with potentionally longterm administration not compromising its original efficacy and subjective tolerance. Anakinra, blocking autonomous inflammatory reaction of the organism via interleukin1 pathway, is a generally accepted first line treatment that should be made available in standard dosing for all Schnitzler patients.

SUMMARY Twenty-five breast cancer patients previously not exposed to adriamycin, were treated with 30 mg/m2/day aclarubicin for four consecutive days. Out of the 19 evaluable cases 1 CR and 2 PR were observed giving an overall remission rate of 16%. No cardiotoxicity was observed. Myelotoxicity and hair loss were mild (WHO grades 1 and 2). Grade 2 and 3 nausea and vomiting occurred frequently.

The primary aim of palliative treatment is to improve the quality of life, followed by prolongation of overall survival. The effective regimens are usually complicated by increased side effects, particularly hematologic. Under these conditions, useful treatment is difficult and less effective.We present the case of a patient with cancer of the abdominal and pelvic cavity (the origin was likely an ovary). The patient was treated with intensive chemotherapy (15 cycles of carboplatin and paclitaxel) and supportive care (30 doses of epoetin alpha and 2 doses of 48MIU G-CSF for neutropenia G4).A good quality of life and long-term persistent complete remission (6 months) was achieved, no transfusion, no hospitalization. Overall survival was 61 months.

High-risk human papillomavirus (HPV) are implicated in the development of a subset of head and neck cancers, especially those arising from the lingual or palatine tonsils. HPV-associated cancer of the head and neck represent a different disease entity from those associated with the traditional risk factors of tobacco and alcohol use. There has been as increase in the annual incidence of HPV-related cancers in Europe and USA in the past years. It has now become clear that a subset of the head and neck tumors is a sexually transmitted disease with distinct pathogenesis and clinical and pathological features. Research efforts are now focusing on deintensification of treatment to reduce treatment associated morbidity. The potential application of HPV targeted terapies in HPV associated cancers is an area of active research.

The number of malignant diseases increases and the question is why. Why is there an increasing incidence of certain cancers and why an increasing number of people dies from them? We do not have a clear answer to these questions. We just know that a development of cancer depends on certain internal predispositions as well as external conditions. We are unable to change our genetic predisposition but we are able, to some extent, influence the intensity of external factors. This paper summarizes information on the effects of external environment on the development of malignant diseases.

One hundred and eleven previously untreated patients with extensive small cell lung cancer were included in a prospective randomized study with the aim to assess the efficacy and tolerance of high-dose epirubicin (120 mg/m2) in combination with either cyclophosphamide (800 mg/m2; arm 1) or cisplatin (60 mg/m2; arm 2). Ninety-six patients were evaluable for response and toxicity and additional 12 patients for toxicity only. The overall response rate (CR+PR) in arm 1 and 2 were 61.4 (27/44) and 67.3% (35/52), respectively. The mean duration of remission was 4.4 months (arm 1) and 4.9 months (arm 2). The mean survival time was 6.6 months in arm 1 and 7.7 months in arm 2. WHO grade 4 toxicity was encountered in 25.5 and 15.8% of patients in arm 1 and 2, respectively. One case of cardiotoxicity resulting in the patient's death was observed in arm 1. Both combinations showed considerable antitumor activity. Toxicity was acceptable.

On the basis of results obtained with oral idarubicin administration in breast cancer, which have shown an established antitumor activity in approximately 28% of cases, this compound was combined with

Head and neck squamous cell cancer (HNSCC) management is evolving rapidly. Approaches under exploration include induction chemotherapy, altered fractionation radiation with chemotherapy, intensity modulated radiation therapy (IMRT) and the use of biologically targeted drugs to enhance radiation. The goal of the new methods is improving the effectivity without increasing the toxicity. This article will focus maily on locally advanced HNSCC, which frequently remains a clinical challenge, review state-of-the-art therapy and introduce promising novel terapies. For the future the incorporation of new agents, the use of novel biomarkers to accurately assess and individualize therapy, and expanded supportive care approaches will play an increasingly important role.

The objective of this trial was to define the antitumor activity and toxicity of etoposide for second-line treatment of patients with bulky ovarian carcinoma. Between February 1, 1986 and November 1, 1988 we recruited 82 patients. Out of them 77 (93.9%) were evaluable for toxicity and 71 (86.6%) for response. Patient characteristics are as follows: median age 57 years (range 15-75), median performance status: WHO 1, prior chemotherapy with more than 3 drugs 24 patients, with previous cisplatin 63 patients, with previous adriamycin 47 patients, with previous irradiation plus chemotherapy 17 patients. The following treatment schedule was applied: each patient started with 150 mg/m2 of etoposide administered i.v. on days 1-3. If this first cycle was well tolerated the dosage was escalated to 200 mg/m2 days 1-3. This higher dosage was then repeated at 4-week intervals. For evaluation of response the WHO criteria were used. One patient (1.4%) achieved complete remission and 5 (7.0%) partial remission. In 48 patients (67.6%) minor response or stabilisation of the disease were observed. Seventeen patients (24%) showed no response. The median duration of remission was 5.5 months (range 2-20). The median duration of stabilisation was 3 months (range 2-24). The median survival time was 10 months with a range of 2-30 months. The myelotoxic side-effects are as follows: WBC less than 2,000 was recorded in 6 patients and greater than 1,000 in 2 patients. Thrombocytopaenia with platelet count less than 50,000 occurred in 1 patient. 26 patients had anaemia WHO grades 2 and 3. Non-haematological toxicity consisted of nausea and vomiting (WHO grade 2:20 patients and grade 3:2 patients), alopecia (WHO grades 2-3:14 and 24 patients, respectively). Though the remission rate in this trial was low, the 10-month median survival with an acceptable quality of life can be taken as a fairly good salvage therapy result.

In a multicentre study patients with liver metastases stratified to the histology of the primary tumour were investigated. A total of 102 patients with colorectal adenocarcinoma, non-small-cell lung cancer, pancreatic cancer, primary liver carcinoma and malignant melanoma were treated with the thioether lipid ilmofosine. The drug was administered orally as a tablet at a dosage of 150-300 mg/day (75 mg/tablet). The tolerability of ilmofosine was poor. There was a dose-limiting gastrointestinal toxicity with nausea, vomiting and loss of appetite (WHO grade II-IV) in 67% of patients. During the period of therapy (1-29 weeks, 8.5 weeks mean) no complete remission and no partial response were observed. We thus conclude that treatment with oral ilmofosine is not effective in patients with liver metastases due to various malignancies.

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 cardiotoxicity, 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.

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%) experimenced 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.

Twenty-five evaluable pediatric patients with histologically proven Burkitt's lymphoma were treated with moderate dose combination chemotherapy consisting of cyclophosphamide, vincristine, methotrexate and cytosine arabinoside (COMA regime) without central nervous system prophylaxis. Complete remission was achieved in 94.1% (16/17) of patients with Stage I, I R, II and III A disease, with disease-free survival of more than 3 years. This protocol was attended by minimal chemotherapeutic toxicity. This combination chemotherapy was ineffective in more advanced disease (Stages III B, IV), major cause of failure being progressive disease with central nervous system involvement. This study showed the effectiveness of moderate dose chemotherapy without CNS prophylaxis in early stage Burkitt's lymphoma including Stage III A and needs for aggressive chemotherapy with CNS prophylaxis in more advanced disease.

Melanoma cells freshly isolated from 63 advanced primary lesions and 103 metastases were analyzed by staining with monoclonal antibodies MEM 28 directed against a 200 kDa antigen present on all leukocytes and tissue macrophages (CD 45), MEM 18 directed against a monocyte antigen of 53 kDa, anti CD 14--Immunotech, Marseille and 3.9 directed against a 150 kDa antigen expressed on monocytes and to even greater degree on most tissue macrophages (CD 11 c). All antibodies showed variable reactivity with melanoma cells, percentage of positive tumor cells ranged from 0 to 70.

On the basis of results obtained with oral idarubicin administration in breast cancer, which have shown an established antitumor activity in approximately 28% of cases, this compound was combined with cyclophosphamide (also given orally) in postmenopausal patients with an unknown or negative steroid receptor status. The study comprised 45 untreated patients out of which 44 were evaluable for response and toxicity. The mean age was 62.5 years (range 51-75). The majority of patients had soft tissue (24) and visceral organ (17) metastases. Idarubicin was administered in one oral daily dose of 45 mg/m2 on day 1; the oral cyclophosphamide dose was 200 mg/m2 daily on days 3, 4, 5 and 6. An objective response to treatment was observed in 41% of patients (18/44, 95% confidence interval 28-56%). Complete remission (lung) was observed in 2 patients (5%), while 16 patients achieved a partial response. Eleven patients showed no change, while 15 patients progressed. A particularly good response was obtained in soft tissue metastases (54%, 13/24) while in visceral organs a response was achieved in 31% of patients (5/16). The remissions lasted 2-14 months (median 7 months), and median survival was 14+ months. Toxicity was mild and the treatment well tolerated. Grade I/II leukopenia was observed in 24% of patients (median WBC nadir 3,100); there were no signs of cardiotoxicity. Grade I and II alopecia was observed in 75% of patients: nausea/vomiting were present in 73% of cases. The results of this study indicate that oral administration of idarubicin and cyclophosphamide produces a valuable antitumorigenic effect in postmenopausal breast cancer patients, particularly in soft tissue metastases. Further randomized studies will be needed to evaluate this treatment approach.

The objective of this trial was to define the antitumor activity and toxicity of etoposide for second-line treatment of patients with bulky ovarian carcinoma. Between February 1, 1986 and November 1, 1988 we recruited 82 patients. Out of them 77 (93.9%) were evaluable for toxicity and 71 (86.6%) for response. Patient characteristics are as follows: median age 57 years (range 15-75), median performance status: WHO 1, prior chemotherapy with more than 3 drugs 24 patients, with previous cisplatin 63 patients, with previous adriamycin 47 patients, with previous irradiation plus chemotherapy 17 patients. The following treatment schedule was applied: each patient started with 150 mg/m2 of etoposide administered i.v. on days 1-3. If this first cycle was well tolerated the dosage was escalated to 200 mg/m2 days 1-3. This higher dosage was then repeated at 4-week intervals. For evaluation of response the WHO criteria were used. One patient (1.4%) achieved complete remission and 5 (7.0%) partial remission. In 48 patients (67.6%) minor response or stabilisation of the disease were observed. Seventeen patients (24%) showed no response. The median duration of remission was 5.5 months (range 2-20). The median duration of stabilisation was 3 months (range 2-24). The median survival time was 10 months with a range of 2-30 months. The myelotoxic side-effects are as follows: WBC less than 2,000 was recorded in 6 patients and greater than 1,000 in 2 patients. Thrombocytopaenia with platelet count less than 50,000 occurred in 1 patient. 26 patients had anaemia WHO grades 2 and 3. Non-haematological toxicity consisted of nausea and vomiting (WHO grade 2:20 patients and grade 3:2 patients), alopecia (WHO grades 2-3:14 and 24 patients, respectively). Though the remission rate in this trial was low, the 10-month median survival with an acceptable quality of life can be taken as a fairly good salvage therapy result.

The purpose of the study was to investigate the antitumour activity and toxicity of high dose (120 mg m-2) single agent epirubicin therapy in untreated extensive small cell lung cancer patients. Out of 80 patients entered, 71 were evaluable for both antitumour activity and toxicity, 4 only for toxicity and 5 were lost for follow-up. The drug possessed a high antitumour activity, the overall response rate was 47.9% (34/71) with 4 complete remissions (CR) and 30 partial remissions (PR). The median remission duration was 3.5 months. Particular drug activity was observed in the primary tumours, lymph nodes and pleural metastases. Toxicity (leukopenia, anaemia, vomiting, reversible rhythmic cardiac disorder, stomatitis) was mild, alopecia was registered less than in adriamycin medication. One fatal congestive heart failure occurred. The actual mean survival time calculated on the basis of the data gained from 64 patients was 7.0 months (range 2-22). The high antitumour activity and no increase in toxicity justify the incorporation of high dose epirubicin into combination therapy.

Multinucleated cells (MC) were counted in cell preparations obtained by dissociation of representative part of tumor lesions immediately after excision. MC were present in almost all specimens examined (39 advanced primary lesions, 90 lymph node metastases and 33 dermal plus subcutaneous metastases); in one third of the samples they were very rare (less than 1% of all cells). There were no significant differences in quantity of MC between primary tumors, node metastases and dermal plus subcutaneous metastases, between node metastases seen early in the course of the disease and those seen later, and between regional node metastases taken from Stage II patients with rapidly progressing disease and regional node metastases taken from patients of the same stage whose disease-free intervals were longer. No unique pattern of similarities or differences in quantity of MC was found when comparing autologous tumor samples excised simultaneously and/or successively during the course of the disease.

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.

Results of a prospective randomized clinical trial conducted by the WHO Collaborating Centers for the Evaluation of Methods of Diagnosis and Treatment of Melanoma are reported. Five-hundred-fifty-three Stage I patients whose limbs were affected entered the study; 267 were submitted to wide excision and immediate node dissection and 286 had wide excision and node dissection at the time clinically positive nodes were detected. Survival curves of the two treatment groups could be superimposed. No subsets of patients benefitted from immediate node dissection. The authors conclude that delayed node dissection is as effective as the immediate dissection in Stage I melanoma of the extremities if the patient can be checked every three months. If the quarterly follow-up is not guaranteed, immediate node dissection is advisable, at least for melanomas thicker than 2 mm.

Aclacinomycin A (ACM) in a daily dose of 30 mg/m2 was infused over 1 h on 4 consecutive days to 50 patients. Myelotoxicity was acceptable, nausea and vomiting was frequent, hair loss was mi

Some cytologic criteria useful for routine examinations in the diagnosis of malignant melanoma are reported and the diagnostic value of the pre-operatory cytologic smears is also emphasized.

553 patients with stage I malignant melanoma of the limbs entered a prospective randomized clinical trial carried out by the W.H.O. Collaborating Centres for Evaluation of Methods of Diagnosis and Treatment of Melanoma from September 1967 to January 1974. 286 patients were submitted to wide excision of primary and node dissection at the time as appearance of regional lymph node metastases and 267 to wide excision and immediate node dissection. Survival was identical in the 2 groups. Different subsets of patients were evaluated to assess whether some groups of patients may benefit from immediate node dissection. As regards sex, females and a significantly higher survival rate than males (p < 0.05), but results were not improved by immediate node dissection. Maximum diameter and elevation of primary melanoma were significantly related to survival but also in these cases immediate node dissection did not achieve better results. 63 patients had an excisional biopsy of their melanoma within 4 weeks before final treatment. This procedure did not worsen survival and also in this case immediate node dissection did not improve survival. 273 cases were classified according to histologic type: survival of superficial spreading and nodular melanoma was not different at a statistically significant level after the 2 treatment modalities. 325 cases were considered classifiable according to Clark's levels, out of these 165 were submitted to immediate node dissection. Neither level III nor level IV cases showed higher survival rate after immediate node dissection. Maximum tumor thickness according to Breslow was evaluated in 338 cases: 188 were submitted to wide excision and immediate node dissection. In no clusters of thickness did the enlarged surgical procedure achieve better results. The authors conclude that there is good evidence that in stage I melanoma of the extremities delayed dissection is as effective as the immediate one in the control of the disease if the patient can be kept under strict clinical control. Immediate node dissection is advisable if the quarterly follow-up is not guaranteed, at least for melanomas thicker than 2 mm.

From 1976 to 1980, 377 randomized patients were entered in a multicentric study supported by the W.H.O. Melanoma Group. In this report, only 196 patients are considered for analysis: 31.6 % were excluded because of inadequate treatment or protocol violations. Three arms of treatment were compared: DTIC alone, DTIC plus bacillus Calmette-Guérin, and DTIC plus Corynebacterium parvum. No significant difference in terms of complete response plus partial response was detected among the three regimens. Twenty-five patients (12.7 %) responded with complete tumor regression, and 18 (9.3 %) with partial regression. Complete plus partial responses were thus achieved in 22 % of evaluable patients. Responders had a longer median survival than nonresponders. Overall median survival was 6 months. Brain metastases were detected in 17 % of the patients. Median time from the beginning of treatment to the diagnosis of CNS involvement was 4 months. There is no evidence that active aspecific immunotherapy added to DTIC increases the response rate in patients with disseminated disease. The toxic effects were acceptable, and no drug-related death was observed.

The therapeutic efficacy of the combination of cyclophosphamide + epirubicin + cisplatin was evaluated in 107 previously treated or untreated patients with advanced ovarian cancer. The overall response rate was 58.8%, complete remission 36.4% (mean duration 7.62 months) and partial remission 22.4% (mean duration – 6.74 months). The response was rated in function of age, menopausal status, performance status and previous therapy. Toxicity (in case of 109 patients) was evaluated according to the WHO recommendation. The similar therapeutic effectiveness and less toxicity of the above drug combination compared to CAP regimen is demonstrated.

We studied the chemo-radiotherapy of testicular tumors in clinical stage III. Our study involved 54 patients with lung metastases of seminoma and nonseminoma, treated with a combination of radiotherapy and chemotherapy. The results obtained have not satisfied our expectations. While in the 16 seminoma patients only 43% overall response rate was obtained (probably due to the bad general condition of the patients who had mostly received previous treatment), in the 38 nonseminoma patients a 63% overall response rate was obtained, with 31% complete remission. In previously untreated patients a 73% overall response rate was obtained at 34% complete remission.

VM 26, a semisynthetic podophyllin derivative (4-demethyl-epipodo-phyllotoxin-beta-d-thenylidine glucoside) has been tested in 67 patients with urinary bladder tumors. In 25 patients with stage T 1 significant prolongation of the disease-free interval was reached. In 25 cases with state T 3-4, the effect of VM 26 was not favorable.

Experiences with cis Platin therapy in cases of ovarian cancers after previous tumorchemotherapy are reported. 23 patients were treated with 100 mg cis Platin (DDP)/m2 (Lachema, CSSR, Brno) in intervals of four weeks following extensive hyperhydratation. We observed following therapeutic effects: CR 4 of 23 pat., PR 11 of 23 pat., NC 3 of 23 pat. and progression in 5 cases. The average remission-time was the best in cases with CR (8,3 month) and the worst in cases without any therapeutic effect (1 month). Side effects observed: severe vomiting was compulsory in all cases. Twice we observed neuro- and ototoxicity after the 5th respectively 6th cyclus. DDP is an effective but also toxic cytostatic drug for treatment of ovarian cancer in the 2nd or 3rd line. It should be used in cases of secondary resistant tumours.

An early and adequate surgical intervention may have a favorable effect on the course of malignant melanoma (m.m.). Despite the focused publicity given to problems relating to m.m., faulty nonradical excisions of suspected pigmented lesions are still performed rather frequently in surgical outpatient departments. One of the reasons may be the rather difficult clinical diagnosis due to pleiomorphism of m.m., but a lack of experience of certain physicians is also responsible. The authors indicate what effective course to pursue in these patients. On the evidence of their set of 48 patients operated upon, they have shown a radical reexcision of the scar with its wide vicinity, following a nonradical intervention, to be justified. In certain cases, it may affect an eventful dissemination of tumorous cases, it may affect an eventual dissemination of tumorous cells in the close vicinity of the scar after an inadequate excision. In addition, they have delimitated indications valid for a radical reexcision.

Fourteen patients with advanced carcinoma of the breast were treated with CAP combination therapy. An objective therapeutic response (partial remissions with a mean duration of 6.3 months) was achieved in 6 of 13 evaluated patients. This response was observed in soft tissue metastases. Nausea and vomiting were found to be the most frequent undesirable side effects in all patients and could not be avoided by administration of antiemetics. In 2 patients mild nephrotoxicity was found without any effects on further therapy. The results of this study were considered as promising; a definitive assessment of the CAP regimen is expected to come from a randomized study which started in the CMEA countries in 1983.

Skin tests with autologous cholesteryl hemisuccinate-treated tumor cells were performed in Stage II malignant melanoma patients. In the majority of cases an evident reaction having features of delayed type hypersensitivity was noted. No significant correlation between this reactivity and subsequent course of the disease was found. The same was true for the results of DNCB and PPD skin testing. An analysis of the results of all three tests in the same patient revealed no prognostic significance of this score either.

A comparison of efficacies of medroxyprogesterone acetate (MPA) and the antiestrogen tamoxifen (TX) in the therapy for advanced breast cancer in patients who had already previously been intensely treated showed that, as to the objective remissions, the two drugs can be looked upon as equivalent. Nevertheless, with MPA a better analgetic and anabolic effect--a marked improvement in the performance status (Karnofsky index)--was achieved.

Forty-eight patients with metastatic breast cancer previously treated with cytostatics (except anthracyclines) underwent peroral treatment with 4-demethoxydaunorubicin (4-DMDR), a new daunorubicin analogue. Forty-three patients received greater than or equal to 2 cycles and have been evaluated. The mean age was 54 years, with 10 premenopausal and 33 postmenopausal patients. All the patients showed progressive disease. Performance status 0-2 (ECOG score) was recorded in 34, and 3 in 7 patients. Soft tissue metastases were recorded in 23, visceral in 10 and bone in 10 patients. 4-DMDR was administered in the dose of 15 mg/m2 perorally daily, on day 1, 2 and 3 (45 mg/m2 per cycle). Since there was no severe toxicity, after 2 cycles the dosage was increased to 60 mg/m2 per cycle. The patients received 2-6 cycles (median 3) and the total cumulative dose ranged from 90 to 300 mg/m2 (median 140 mg/m2). Objective response was observed in 10 patients (1 complete remission, 9 partial remissions) with a response rate of 23% (10/43). Soft tissue metastases were most responsive (8/23-35%). Two responses were observed in visceral organs. Response lasted 2-6+ months (median 4 months). Toxic side effects have been mild with myelotoxicity (grade I-II) observed in 23% of patients. Alopecia (grade 1-15 patients, grade II and III = 4 patients) was moderate. Nausea and vomiting (grade I-II) was present in 60% of patients. In all the patients MUGA scans (left ventricular ejection fraction) were in normal range, however, reversible ECG changes have been recorded in 4 patients (grade I = 3, grade II = 1). All the changes appeared on the 3rd day of the cycle but became normal before starting a new cycle. In conclusion, it should be emphasized that 4-DMDR administered perorally (45 mg/m2 per cycle) in previously treated (except anthracycline) metastatic breast cancer patients showed antitumor efficacy with a low incidence of toxic side effects. Further clinical studies, possibly with the dose escalation in the schedule we have used, will be needed in previously untreated breast cancer patients to determine exact antitumor activity of this new daunorubicin analogue.

Cytology in malignant melanoma of the skin is a useful method, which alone yields in many cases enough diagnostic informations for a therapeutical approach. It is of a special importance in cases with marked anisocytosis of cells and with large, sometimes polynuclear cells and with cells with melanotic pigment. In cases with middle-sized apigmented cells of epitheloid appearance it should be always completed by biopsy, which, in these cases predominates over cytology. Combination of both methods brings a more substantial elucidation of diagnosis.