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Background: Novel therapeutic approaches and new compounds during the last decade have prolonged survival of breast cancer patients with metastatic disease, resulting in higher incidence of central nervous system (CNS) metastases. Many of these patients live longer than expected. Patients and methods: We reviewed breast cancer patients with brain metastases from our department, living longer than 1 year. Our purposes were to present patient and treatment characteristics and correlate them with disease outcome. Moreover, we aimed at reviewing the current literature. Results: We detected 20 women with brain metastases from breast cancer, living longer than 1 year. The mean age was 41 years (range 22-61 years). One (5%) woman had luminal A breast cancer type, four (20%) patients had luminal B and HER2 negative, nine (45%) patients luminal B and HER2 positive, four (20%) patients HER2 enriched and two (10%) patients had triple-negative breast cancer. Most of them (70%) had infiltrating ductal histological type and grade 3. Moreover, the majority had known metastatic disease when brain metastases appeared. The most common sites of disease were lung, liver and bone. Median time from breast cancer diagnosis until the presence of CNS metastases was 44 months (range 6-204 months). The progression free survival (PFS) of the most chemotherapeutic schedules was according to the literature. However, PFS of some compounds exceeded all expectations. Median time of survival was 25 months (range 13-116 months). Ten patients are still alive, having achieved a median survival rate of 35 months (range 17-78 months). Conclusion: The combination of surgery, radiotherapy, chemotherapy and anti HER2 treatments is at present the best way to extend the OS and improve the quality of life of breast cancer patients with brain metastases. Prognostic markers for assessing brain metastases are required. Application of prophylactic treatment for these patients is under consideration.

Background: The HER2 gene has been established as a valid biological marker for the treatment of breast cancer patients with trastuzumab and probably other agents, such as paclitaxel and anthracyclines. The TOP2A gene has been associated with response to anthracyclines. Limited information exists on the relationship of HER2/TOP2A gene status in the presence of centromere 17 (CEP17) gain with outcome of patients treated with anthracycline-containing adjuvant chemotherapy.Methods: Formalin-fixed paraffin-embedded tumor tissue samples from 1031 patients with high-risk operable breast cancer, enrolled in two consecutive phase III trials, were assessed in a central laboratory by fluorescence in situ hybridization for HER2/TOP2A gene amplification and CEP17 gain (CEP17 probe). Amplification of HER2 and TOP2A were defined as a gene/CEP17 ratio of >2.2 and ≥2.0, respectively, or gene copy number higher than 6. Additionally, HER2, TopoIIa, ER/PgR and Ki67 protein expression was assessed by immunohistochemistry (IHC) and patients were classified according to their IHC phenotype. Treatment consisted of epirubicin-based adjuvant chemotherapy followed by hormonal therapy and radiation, as indicated.Results: HER2 amplification was found in 23.7% of the patients and TOP2A amplification in 10.1%. In total, 41.8% of HER2-amplified tumors demonstrated TOP2A co-amplification. The median (range) of HER2, TOP2A and CEP17 gain was 2.55 (0.70-45.15), 2.20 (0.70-26.15) and 2.00 (0.70-26.55), respectively. Forty percent of the tumors had CEP17 gain (51% of those with HER2 amplification). Adjusting for treatment groups in the Cox model, HER2 amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification were not associated with time to relapse or time to death.Conclusion: HER2 amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification were not associated with outcome in high-risk breast cancer patients treated with anthracycline-based adjuvant chemotherapy.Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12611000506998 and ACTRN12609001036202. © 2013 Fountzilas et al.; licensee BioMed Central Ltd.

362 evaluable node-positive patients with stage II breast cancer were randomized, receiving either 6 cycles of conventional CMF or 6 cycles of the combination of cyclophosphamide (500 mg/m2), mitoxantrone (Novantrone 10 mg/ m2), and fluorouracil (500 mg/m2; CNF). After a median follow-up of 51 months, 64 (36%) patients relapsed in the CMF group and 60 (33%) in the CNF group (p = 0.8276). By Cox multivariate analysis, tumor size, menopausal status and number of involved nodes were retained as independently significant variables. Toxicities were remarkably similar in both groups. It appears that after a median follow-up of 51 months there is no significant difference in relapse-free survival between node-positive patients with breast cancer who received either 6 cycles of the conventional CMF or the CNF combination as adjuvant treatment. © 1996 S. Karger AG, Basel. 53 2 137 146

We present a case of interstitial nephritis and nephrogenic diabetes insipidus (NDI) in a patient treated with pemetrexed (500 mgm2) for non-small cell lung cancer. Renal impairment and diabetes insipidus appeared after the first treatment cycle while he totally received four cycles of chemotherapy. There was not any significant myelosuppression and the patient was on regular supplementation with folic acid and vitamin B12. He was not on any other medications and he did not receive any nephrotoxic agents. Kidney biopsy showed acute tubular necrosis together with interstitial inflammatory infiltrate of mononuclear cells and interstitial fibrosis occupying 25% of the cortex. There was not any improvement of renal function after a 2-week trial of oral prednisone. In the present case report, we review the literature for pemetrexed-induced renal toxicity and the possible mechanisms involved. © 2010 Informa UK Ltd.

The possibility of increased risk for osteoporosis in breast cancer patients treated with tamoxifen was investigated. 26 patients aged 41-65 years without skeletal metastases were studied. All patients were treated with 20 mg/d tamoxifen for a mean time of 22 months. The data obtained by in vivo neutron activation analysis of the phosphorus content in hands, were supplemented with data obtained by single photon absorptiometry in the forearm and radiographic morphometry. Comparison of the data with that of age and sex matched normal controls showed that breast cancer patients treated with tamoxifen are not prone to osteoporosis. 65 773 417 420

It is controversial whether non-small cell lung cancer (NSCLC) in the elderly constitutes a distinct clinico-biological entity compared to younger counterparts. As reported data are scant and discordant, we sought to analyze retrospectively the medical records of Hellenic NSCLC patients aged >70 years and compare them with those of age (70-45 years) and younger (

In a pilot phase II study we have treated 25 patients with small cell lung cancer by utilizing 3 non-cross resistant drug regimens given in a sequential fashion in combination with radiotherapy to the primary tumor. VAC regimen (etoposide, doxorubicin, cyclophosphamide) was planned to induce major cytotoxity, CVM (cisplatin, vincristin, high-dose methotrexate) to intensify cell killing and MCP (mitomycin-C, CCNU, procarbazine) to maintain response. Overall response rate was 88% with 24% complete and 64% partial responders. Duration of response was 8.3+ months. Median survival was 12 months, 17 for complete and 10.5 months for partial responders. Sixty-one per cent survived for more than one year, while one patient is alive with no evidence of disease 30 months after diagnosis. In conclusion, sequential chemotherapy with non-cross resistant cytostatic agents in small cell lung cancer did not offer superior results compared to any other form of treatment. © 1991. 7 5 279 283

Chemotherapy is an established modality in the management of patients with advanced gastric cancer but the optimal regimen has not been defined yet. Platinum and the anthracyclines and more recently docetaxel have shown activity in this tumor. The primary objective of this phase II study was to assess the efficacy and safety of an intensified regimen of weekly docetaxel/epirubicin/ carboplatin (DECb) with growth factor support in previously untreated patients with advanced gastric cancer. A total of 72 patients with measurable disease received docetaxel at a dose of 30 mg/m2, epirubicin at a dose of 30 mg/m2 and carboplatin to a target area under the curve (AUC) of 2, every week for 6 consecutive weeks followed by 2 weeks' rest, with filgrastim support. Analysis was performed on an intention to treat basis. The main toxicity was hematologic with grade 3/4 neutropenia occurring in 35% of the patients. Other grade 3/4 toxicities included anemia (7%), thrombocytopenia (14%) and leucopenia (26%). The relative dose intensity of docetaxel and epirubicin was 62%. The overall response rate was 21%, the median time to tumor progression was 4.1 months and the median survival 7.3 months. Intensified weekly treatment with DECb has modest activity in the treatment of advanced gastric cancer. Myelotoxicity limits adequate drug delivery. © Humana Press Inc. 2007.

BACKGROUND: Non-small cell lung cancer (NSCLC) in young patients is uncommon and is thought to constitute a distinct oncological entity with characteristic clinicopathological patterns. Since the reported data are scant and discordant, the presentation, management and outcome data of NSCLC patients aged under 45 years of age were analyzed and compared with those of patients over 45 years old. Prognostic factors for risk classification were also evaluated. MATERIALS AND METHODS: The data were abstracted from the Hellenic Cooperative Oncology Group (HeCOG) cancer registry database. The presentation, management and outcome data of patients with histologically confirmed NSCLC, managed from 1989 until 2004 in HeCOG participating centers, were retrospectively analyzed. The clinicopathological characteristics of patients aged < and > than 45 years old were compared and evaluated for prognostic significance regarding outcome. RESULTS: The data for NSCLC patients (1906), of whom 115 were aged

Background: A phase II study was conducted to evaluate the efficacy and toxicity of the combination of gemcitabine (GEM) and pegylated liposomal doxorubicin (PLD) in patients with platinum- and/or taxane-resistant/refractory advanced epithelial ovarian cancer (AEOC). Patients and Methods: Patients (pts), who had been treated with platinum or paclitaxel and met the criteria of resistant/refractory AEOC, received GEM 650 mg/m2 days 1 and 8 and PLD 25 mg/m2 day 1 every 4 weeks up to a total of 6 cycles, unless disease progression or adverse effects prohibited further therapy. Results: Thirty-seven patients entered the study. There was 1 complete (3%) and 7 partial responses (19%) for an overall response rate of 22%. Two patients had stable disease (5.5%). After a median follow-up of 16.2 months, the median survival was 8.4 months and time to treatment failure 2.7 months. The most frequent severe toxicity was myelosuppression recorded in 13 (35%) patients. Severe stomatitis was recorded in only 2 (5%) cases and severe palmar-plantar erythrodysesthesia in 1 patient. One severe allergic reaction (grade 4) to PLD was recorded following the third cycle of treatment. Conclusion: The combination of GEM and PLD in patients with AEOC, who are resistant/refractory to platinum and/or Taxanes, did not show any superiority over monotherapy. However, in view of the acceptable toxicity profile, the above combination may deserve further investigation in a randomised setting. 25 4 3103 3108

INTRODUCTION: Patients with cavitating squamous lung carcinoma (cSLC) are believed to harbor aggressive, chemoresistant disease with distinct features and fare poorly. We retrospectively analyzed radiologic, histologic, and clinical features of patients with cSLC and solid SLC (sSLC) from the patient registry of four Hellenic Cooperative Oncology Group (HeCOG) cancer centres in an effort to detect distinct characteristics of cSLC. PATIENTS AND METHODS: 37 cSLC and 212 sSLC patients, most of them male smokers, aged more than 60, treated with resection and/or chemotherapy/radiotherapy were included in the analysis. Disease stage, histologic differentiation and lymphatic/vascular invasion, pre-diagnosis symptoms and their duration, tumor size, site and associated features, metastatic sites, chemotherapy administered, responses and duration as well as time to treatment failure, and overall survival were analyzed for significant differences between the two patient groups. RESULTS: Statistically significant differences (two-sided P < 0.05) in patients with cSLC were found for: locally advanced (IIIB) or metastatic (IV) disease (76.5%) at presentation, longer duration of pre-diagnosis symptoms (mean 10 months), more frequent manifestation of fever, cough, weight loss, poor tumor differentiation, lower lobe primary, absence of atelectasis and satellite lesions. Objective response rates (33% for cSLC versus 32% for sSLC) and response duration (median 6 versus 5 months) were no different in the two patient groups. Median time to treatment failure (TTF) and overall survival (OS) were 10 and 13 months for cSLC patients, whereas 12 and 18 months for sSLC patients. Two-year TTF and OS rates were 18.5% and 33.5% for cSLC, while they were 19.3% and 40% for sSLC. No statistically significant differences were observed in any survival curves. CONCLUSION: Patients with cSLC present with high grade tumors that may initially simulate infectious processes, leading to late diagnosis despite long standing symptoms and presentation with advanced disease. In view of lack of evidence for differential disease course, increased chemoresistance and inferior outcome in comparison to sSLC patients, the definition of cavitating pulmonary carcinoma as a distinct clinical subentity cannot be supported. Lung Cancer

Introduction: Patients with cavitating squamous lung carcinoma (cSLC) are believed to harbor aggressive, chemoresistant disease with distinct features and fare poorly. We retrospectively analyzed radiologic, histologic, and clinical features of patients with cSLC and solid SLC (sSLC) from the patient registry of four Hellenic Cooperative Oncology Group (HeCOG) cancer centres in an effort to detect distinct characteristics of cSLC. Patients and methods: 37 cSLC and 212 sSLC patients, most of them male smokers, aged more than 60, treated with resection and/or chemotherapy/radiotherapy were included in the analysis. Disease stage, histologic differentiation and lymphatic/vascular invasion, pre-diagnosis symptoms and their duration, tumor size, site and associated features, metastatic sites, chemotherapy administered, responses and duration as well as time to treatment failure, and overall survival were analyzed for significant differences between the two patient groups. Results: Statistically significant differences (two-sided P

A 76-year-old woman with atypical hemorrhagic Kaposi sarcoma is presented. The patient was treated with recombinant interferon alpha-2b (3,000,000 IU) subcutaneously, three times weekly for 6 months and twice weekly as maintenance dose for 14 months with excellent response and no recurrence after a 7 years of follow-up. Eur J Dermatol

SUMMARY: The present randomized phase III trial was designed to detect a 15% benefit in relapse-free survival (RFS) or overall survival (OS) from the incorporation of adjuvant tamoxifen to the combination of CNF [cyclophosphamide, 500 mg/m2; mitoxantrone (Novantrone), 10 mg/m2; fluorouracil, 500 mg/m2 chemotherapy and ovarian ablation in premenopausal patients with node-positive breast cancer and conversely from the incorporation of CNF chemotherapy to adjuvant tamoxifen in node-positive postmenopausal patients. From April 1992 until March 1998, 456 patients with operable breast cancer and one to nine infiltrated axillary nodes entered the study. Premenopausal patients were treated with six cycles of CNF chemotherapy followed by ovarian ablation with monthly injections of triptoreline 3.75 mg for 1 year (Group A, 84 patients) or the same treatment followed by 5 years of tamoxifen (Group B, 92 patients). Postmenopausal patients received 5 years of tamoxifen (Group C, 145 patients) or 6 cycles of CNF followed by 5 years of tamoxifen (Group D, 135 patients). Adjuvant radiation was administered to all patients with partial mastectomy. After a median follow-up period of 5 years, 125 patients (27%) relapsed and 79 (17%) died. The 5-year actuarial RFS for premenopausal patients was 65% in Group A and 68% in Group B (p = 0.86) and for postmenopausal patients 70% in Group C and 67% in Group D (p = 0.36). Also, the respective OS rates were 77% and 80% (p = 0.68) for premenopausal and 84% and 78% (p = 0.10) for postmenopausal patients. Severe toxicities were infrequently seen, with the exception of leukopenia (18%), among the 311 patients treated with CNF. In conclusion, the present study failed to demonstrate a 15% difference in RFS in favor of node-positive premenopausal patients treated with an additional 5 years of tamoxifen after CNF adjuvant chemotherapy and ovarian ablation. Similarly, six cycles of CNF preceding 5 years of tamoxifen did not translate to a 15% RFS benefit in node-positive postmenopausal patients. Am J Clin Oncol

There is some evidence that taxanes and gemcitabine are effective antitumor agents against small-cell lung cancer (SCLC). A total of 20 chemotherapy-naive patients with extensive disease (ED) SCLC, were treated as a part of the first step of a phase II study, with docetaxel 50 mg/m2 and gemcitabine 1000 mg/m2, both administered on day 1 and 8 every 3 weeks up to a total of six cycles. For patients who progressed after the first cycle or had stable disease after the second cycle of chemotherapy, protocol treatment was stopped and further treatment with the standard cisplatin or carboplatin-etoposide combination was administered. Patients were in the vast majority male smokers with a good performance status. A total of 72 cycles was delivered while patients managed to receive the 78 and 84% of the planned dose of docetaxel and gemcitabine, respectively. Only six patients responded partially and the trial ended prematurely since at least seven responses were required among the first 19 patients. With a median follow-up of 13 months, median time to progression (TTP) was 8 months and median survival 9.6 months. Hematological and non-hematological toxicity was generally acceptable while patients tolerated their treatment reasonably well. In conclusion, docetaxel-gemcitabine showed a modest response rate in chemotherapy-naive patients with ED SCLC. © 2003 Elsevier Science Ireland Ltd. All rights reserved. 41 1 107 111

There is some evidence that taxanes and gemcitabine are effective antitumor agents against small-cell lung cancer (SCLC). A total of 20 chemotherapy-naive patients with extensive disease (ED) SCLC, were treated as a part of the first step of a phase II study, with docetaxel 50 mg/m(2) and gemcitabine 1000 mg/m(2), both administered on day 1 and 8 every 3 weeks up to a total of six cycles. For patients who progressed after the first cycle or had stable disease after the second cycle of chemotherapy, protocol treatment was stopped and further treatment with the standard cisplatin or carboplatin-etoposide combination was administered. Patients were in the vast majority mate smokers with a good performance status. A total of 72 cycles was delivered while patients managed to receive the 78 and 84% of the planned dose of docetaxel and gemcitabine, respectively. Only six patients responded partially and the trial ended prematurely since at least seven responses were required among the first 19 patients. With a median follow-up of 13 months, median time to progression (TTP) was 8 months and median survival 9.6 months. Hematological. and non-hematological toxicity was generally acceptable while patients tolerated their treatment reasonably well. In conclusion, docetaxel-gemcitabine showed a modest response rate in chemotherapy-naive patients with ED SCLC. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

This trial was conducted by the Hellenic Cooperative Oncology Group to improve the responses and survival in small cell lung cancer with a good prognosis, using a weekly intensive chemotherapy with alternated non-cross-resistant myelosuppressive agents. Patients were classified into two groups; group A consisted of those who received the initial designed regimen (29 patients), and group B consisted of those who received the more intensified regimen that increased by 25% the doses of carboplatin, epirubicin, and ifosfamide, and by 33% the doses of etoposide given on days 1, 2, and 3 with prophylactic granulocyte colony-stimulating factor support. Chemotherapy in group A consisted of carboplatin 150 mg/m2 in 250 ml of 5% dextrose in water as an 1-hour infusion on day 1, etoposide 75 mg/m2 in 250 ml normal saline as an 1-hour infusion on days 1 and 2 alternating with epirubicin 30 mg/m2 intravenous push on day 8, and ifosfamide 2 g/m2 in 500 ml 5% dextrose in water as a 2-hour infusion with mesna protection on day 8. Responding patients with limited disease were also treated with thoracic irradiation. Those who achieved complete response received prophylactic cranial radiotherapy. In group A, the overall response rate was 79.3%, with a 27.6% complete response rate, a median time to progression of 5.71 months, and a median survival of 8.3 months. For patients with limited disease, the response rate was 75%, with a 40% complete response rate, a median time to progression of 5.87 months, and a median survival of 10.98 months. The respective numbers for extensive disease were 89% (only partial responses), 4.82 months, and 5.67 months. The toxicity was mild and manageable. There were no dose reductions or treatment delays. In view of the excellent tolerability and the rather low efficacy of the initial regimen, we decided to administer the more intensified one with granulocyte colony-stimulating factor support. In Group B, the overall response rate was 91.8%, with a 45.9% complete response rate, a median time to progression of 7.05 months, and a median survival of 10.16 months. For limited disease, the response rate was 93%, with a 52% complete response rate, a median time to progression of 7.05 months, and a median survival of 10.49 months. The respective numbers for extensive disease were 88% (25% complete response), 6.82 months, and 9.02 months. The toxicity of this more intensified regimen was more severe but acceptable. Myelosuppression was the main toxicity. However, grade 3-4 febrile neutropenia requiring hospitalization occurred only in 6% of patients. The relative dose intensity was 91%, probably the result of the prophylactic use of granulocyte colony-stimulating factor. The differences in response rate, time to progression, and survival were not statistically significant between the two groups. There were statistically significant differences in the response rate (p = 0.019) and survival rate (p = 0.001) between limited disease and extensive disease only in group A. In conclusion, this weekly, alternated regimen, specifically the intensified regimen, appears to be very active and well tolerated in patient who have small cell lung cancer with a good prognosis. However, despite the high efficacy, this study failed to show any survival advantage as compared with that obtained with the standard treatment for small cell lung cancer. Am J Clin Oncol

This is a continuation of a HeCOG previous trial utilizing carboplatin and vindesine in conventional doses as a non-toxic regimen provided easily on an outpatient basis in NSCLC. In the present study we investigated whether an intensified dose-carboplatin could yield a better response. Carboplatin at a dose of 450 mg/m2 dose in combination with vindesine 3 mg/m2 every three weeks and GM-CSF support was used in a phase II study to treat 44 patients with non-small cell lung cancer (NSCLC). As compared to our previous study carboplatin dose intensity was increased from 75 mg/m2/wk to 150 mg/m2/wk. Six patients (13.6%) responded to treatment and all were partial responders. The median duration of response was 5 months (range 1.5-9 month). After a retrospective analysis a dose response effect was not evident at different carboplatin AUC doses. Twenty patients (45.45%) experienced thrombocytopenia and seventeen patients (38.6%) anemia as major toxicities. This study shows that in NSCLC a dose-response effect does not exist between carboplatin dose intensification and response rate cannot be traced. 16 1 91 94

This is a continuation of a HeCOG previous trial utilizing carboplatin and vindesine in conventional doses as a non-toxic regimen provided easily on an outpatient basis in NSCLC. In the present study we investigated whether an intensified dose-carboplatin could yield a better response. Carboplatin at a dose of 450 mg/m2 dose in combination with vindesine 3 mg/m2 every three weeks and GM-CSF support was used in a phase II study to treat 44 patients with non-small cell lung cancer (NSCLC). As compared to our previous study carboplatin dose intensity was increased from 75 mg/m2/wk to 150 mg/m2/wk. Six patients (13.6%) responded to treatment and all were partial responders. The median duration of response was 5 months (range 1.5-9 month). After a retrospective analysis a dose response effect was not evident at different carboplatin AUC doses. Twenty patients (45.45%) experienced thrombocytopenia and seventeen patients (38.6%) anemia as major toxicities. This study shows that in NSCLC a dose-response effect does not exist between carboplatin dose intensification and response rate cannot be traced. J Exp Clin Cancer Res

Thirty-four patients with advanced malignant melanoma were treated with recombinant alpha-interferon (IFN) and chemotherapy consisting of carboplatin, vinblastine, and bleomycin (CVB). CVB was given for four cycles and IFN for 1 year or until progression. Of the 34 analyzed patients, 17 (50%) achieved an objective response, including two complete (6%) and 15 partial responses (44%). Responses were noted in cutaneous, lymph node, and pulmonary sites, with a median time to disease progression of 5 months (range, 3-20 months). The median survival from onset of therapy was 8 months (range, 1-22 months) for the 34 patients. Ninety-four percent of the patients experienced flu-like symptoms and 82% fatigue or weakness. Leukopenia grade 3-4 was observed in four patients (12%). There were two toxicity-related deaths (6%); one from bleomycin-induced pneumonitis and one from neutropenic sepsis. It is concluded that the addition of IFN to CVB regimen, in this study, showed no apparent advantage on response rates, disease-free interval, or survival. The observed treatment-related mortality was unacceptably high. IFN administered as maintenance therapy following CVB conferred no survival benefit. Am J Clin Oncol

We compared, in a multicentric randomised prospective study, the efficacy and toxicity of carboplatin 400 mg/m2 as a single agent (CB) to a combination of carboplatin 300 mg/m2, epirubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (CB-EC) in advanced ovarian cancer patients. The treatment was scheduled to be administered every 3 weeks for six courses. Following initial laparotomy and cytoreductive surgery, 130 previously untreated patients entered the study. 73 patients were treated with carboplatin alone while 57 received the combination chemotherapy. In the majority of the patients, the regimens had to be given every 4 weeks due to myelosuppression. Nausea, vomiting and alopecia were more severe in the CB-EC arm. Overall, clinical complete response was observed in 73 (56%) and partial response in 20 (15%) patients. The median time to progression was 16.89 months and median survival was 29.54 months. No significant differences in response rate, time to progression, disease-free survival and overall survival were observed between the two treatment arms. The prognostic role of residual disease after initial surgery, complete remission at second-look laparotomy, tumour stage and performance status was confirmed. Eur J Cancer

We compared, in a multicentric randomised prospective study, the efficacy and toxicity of carboplatin 400 mg/m(2) as a single agent (CB) to a combination of carboplatin 300 mg/m(2), epirubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (CB-EC) in advanced ovarian cancer patients. The treatment was scheduled to be administered every 3 weeks for six courses. Following initial laparotomy and cytoreductive surgery, 130 previously untreated patients entered the study. 73 patients were treated with carboplatin alone white 57 received the combination chemotherapy. In the majority of the patients, the regimens had to be given every 4 weeks due to myelosuppression. Nausea, vomiting and alopecia were more severe in the CB-EC arm. Overall, clinical complete response was observed in 73 (56%) and partial response in 20 (15%) patients. The median time to progression was 16.89 months and median survival was 29.54 months. No significant differences in response rate, time to progression, disease-free survival and overall survival were observed between the two treatment arms. The prognostic role of residual disease after initial surgery, complete remission at second-look laparotomy, tumour stage and performance status was confirmed.

In this report the histopathology and the natural history of cutaneous lymphocytic vasculopathy (lymphocytic vasculitis) in patients with lymphoproliferative diseases, is described. Between January 1986 and June 1992,116 patients with non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemias (CLL) were followed. Among them 3 patients with NHL, one with angioimmunoblastic lym-phadenopathy/lymphoma and 7 with CLL developed cutaneous vasculitic changes during the course of their disease (incidence of 9.5% All patients had advanced stage disease. Lymphomas were of B-cell origin and either low or intermediate grade. The median time between the diagnosis of NHL or CLL and the appearance of skin manifestations was 18 months. Recurrent vasculitic changes involving exclusively the skin, was characterized by a (maculo)papular rash, most commonly found in the upper and lower extremities. Pruritus of varying intensity was present in 82% of the patients. In the biopsy, all had perivascular and/or vessel wall lymphocytic infiltration of the dermis with occasional red cell extravasation. Immunohistochemical staining revealed that these infiltrates were mainly composed of T-lymphocytes. We conclude, that cutaneous lymphocytic vasculopathy is a relatively common paraneoplastic skin manifestation in patients with lymphoproliferative diseases and histologically is characterized as lymphocytic vasculitis with (peri)vascular infiltration by non-malignant T lymphocytes. © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted. 16 5-6 477 482

The delivery of high‐dose epirubicin in patients with advanced breast cancer usually entails serious myelotoxicity and frequent treatment delays. Concurrent administration of G‐CSF probably allows the administration of epirubicin on schedule with minimal morbidity. From August 1990 to February 1992, 42 women with advanced breast cancer were treated with six cycles of epirubicin 110 mg/m2 every 4 weeks. Filgrastim 5 μg/kg per day for 14 days was administered subcutaneously starting 24 hours after chemotherapy. All patients had multiple metastatic sites, and 39 had visceral metastases. All cases were evaluable for response, toxicity, and survival. Treatment was delayed in only two cases. The actually administered average dose per unit time per patient amounted to 99.6% of the dose prescribed by the protocol. Two (4.5%; 95% confidence interval [C.I.] 0–16%) patients demonstrated a complete response and 14 (33%; 95% C.I. 19–49%) a partial response. Median time to progression was 31 weeks and median survival was 60 weeks. Severe granulocytopenia was seen in six patients; stomatitis and diarrhea in one patient each. Myoskeletal pain was noticed in 23 (55%) patients, while cardiac problems were reported in 3 cases. The present study shows that the prophylactic use of r‐met‐hu G‐CSF allows the administration of high‐dose epirubicin every 4 weeks with minimal morbidity and an improved quality of life. © 1995 Wiley‐Liss, Inc. Copyright © 1995 Wiley‐Liss, Inc., A Wiley Company 24 1 23 28

Purpose: To compare the efficacy and toxicity of etoposide and cisplatin (EP) with etoposide and carboplatin (EC) in combination with irradiation in small-cell lung cancer (SCLC). Methods: Previously untreated patients (pts) with SCLC and measurable or evaluable disease were randomized to receive either cisplatin 50 mg/m2 on days 1-2 or carboplatin 300 mg/m2 on day 1, both combined with etoposide 300 mg/m2 on days 1-3 every 21 days for 6 treatment cycles. The vast majority of responding limited disease (LD) pts and complete responders (CR) with extensive disease (ED), also received thoracic irradiation (TI) and prophylactic cranial irradiation (PCI) concurrently with the third cycle. Results: Of the 147 patients registered, 143 were eligible; median performance status (PS, WHO) was 1, and tumour stage was LD in 41 pts of each treatment group. The mean delay between cycles was 8 days in the EP group and 9 in the EC group increasing in both arms with the number of treatment courses. The drug dose administered per unit time as a proportion of the protocol dose was 74% and 80% for the two groups respectively. Leukopenia, neutropenic infections, nausea, vomiting, neurotoxicity and hyperergic reactions were more frequent and/or severe in the EP group. The CR rates were 57% and 58% for EP and EC respectively. Median survival for all pts was 12.5 and 11.8 months, respectively. Conclusion: Both treatments proved to be effective, with no differences in response and survival between the two treatment arms. The EC regimen was associated with significantly less toxicity. © 1994 Kluwer Academic Publishers. 5 7 601 607

In an effort to investigate a regimen less toxic and more convenient than cisplatin combinations, 50 patients with non-small cell lung cancer (NSCLC) were treated in a Phase II study with carboplatin and vindesine. Carboplatin 300 mg/m2 every 28 days and vindesine 3 mg/m2 every 2 weeks were administered on an outpatient basis. Eight patients had a partial response of their disease (16%, confidence limits 7-29%). Mean duration of response was 4.5+ months (1 ± 8). Toxicity, mainly of grade I-II, was noticed in 4-28% of the patients. The most common side effect was mild to moderate leukopenia (28%). The combination of carboplatin and vindesine at the above doses was very well tolerated. Although the response rate was relatively low, the survival in this patient population was similar to other cisplatin-containing regimens. © 1993. 10 1-2 85 89

Summary— In a case of endometrioid carcinoma of the prostate the expression of Leu7 and prostatic specific antigen (PSA) was studied immunohistochemically on paraffin sections. The same markers were studied in 14 cases of prostatic cancer and 14 cases of uterine endometrial carcinoma. Endometrioid carcinoma of the prostate was negative for Leu7 and PSA, while all prostatic cancer specimens were positive for the above markers. All uterine endometrial carcinomas were negative for PSA and only a small percentage of cells in 4 specimens were positive for Leu7. The absence of Leu7 and PSA in this case of endometrioid carcinoma strongly suggests a müllerian origin. © 1993 British Journal of Urology 71 3 309 312

The current study has prospectively investigated the incidence and course of ocular toxicity after low‐dose tamoxifen treatment. Sixty‐three patients with cancer who could be examined were analyzed. Tamoxifen was administered on a 20‐mg daily dose. Median duration of treatment was 25 months. Median total tamoxifen dose was 14.4 gr. Four patients had retinopathy and/or kera‐topathy 10, 27, 31, and 35 months, respectively, after tamoxifen initiation (an incidence of 6.3%). Ophthalmo‐logic findings consisted of decreased visual acuity, bilateral macular edema, yellow‐white dots in the para‐macular and fovea areas in all patients as well as corneal opacities in one patient. After tamoxifen withdrawal almost all ocular abnormalities were found to be reversible, except for the retinal opacities. This is the first prospective study in the literature indicating that even conventional low‐dose tamoxifen treatment can induce ocular toxicity. In addition, the authors review and discuss the literature of the last decades. Copyright © 1992 American Cancer Society 69 12 2961 2964

Ann Oncol

We present here two cases of extraskeletal Ewing's sarcoma, the first in a 50-year-old female and the second in a 25-year-old male. We discuss the clinical picture, histopathology and therapeutic management. The literature is also reviewed, with major emphasis on the treatment of this rare disease. Eur J Surg Oncol

We present here two cases extraskeletal Ewing's sarcoma, the first in a 50-year-old female and the second in a 25-year-old male. We discuss the clinical picture, histopathology and therapeutic management. The literature is also reviewed, with major emphasis on the treatment of this rare disease. 17 3 308 312

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