Paclitaxel and carboplatin in pretreated advanced gastric cancer: a phase II study.

In the present study, the combination of paclitaxel and carboplatin was applied in the treatment of gastric carcinoma. This cytotoxic combination has been an effective regimen with acceptable toxicity in ovarian, lung and head and neck cancers. We evaluated 47 patients (37 male, 10 female), all with advanced disease and all having undergone prior chemotherapy treatment. All patients had disease progression or no response to the prior treatment. Forty-four patients had undergone a previous gastrectomy for gastric adenocarcinoma and 3 patients were inoperable at diagnosis. Paclitaxel 175 mg/m2 was administered as a three-hour infusion, followed by carboplatin 5 AUC infused for 90 min. Thirteen (27.66%) patients showed partial response with a median survival of 10 months; 3 (6.38%) patients showed minor response and 13 patients, stable disease with clinical benefit. The median survival of patients with minor response and disease stability was 6 months. Eighteen (38.29%) patients had disease progression with a median survival of 3 months. It appears that in advanced cancer patients, the paclitaxel-carboplatin combination is an effective second-line treatment, resulting in partial response and disease stability in 61% of patients as well as in a prolongation of median survival.     

Ki-67 proliferation index: correlation with prognostic parameters and outcome in multiple myeloma

The nuclear protein Ki-67 is a proliferation index, as it is expressed only by dividing cells. In this study, we investigated the clinical significance of Ki-67 determination on bone marrow biopsies of 35 patients with newly diagnosed multiple myeloma (MM). We examined the correlation of Ki-67 with other MM proliferation-related factors: interleukin-6 (IL-6), IL-10, bone marrow infiltration by plasma cells, serum lactate dehydrogenase (LDH), and beta 2 microglobulin (b2M). Ki-67 expression was also correlated with the survival rate of the patients. The results showed that Ki-67 expression increases with increasing stage of disease according to Durie-Salmon (classification stage III vs. I and II, p < 0.001). Furthermore, infiltration, IL-6, LDH, and b2M increase significantly with advancing stage of disease (p < 0.004). All parameters studied were significantly higher in patients versus controls. Ki-67 correlated with IL-6 (r: 0.422, p < 0.01), LDH (r: 0.437, p < 0.01), and b2M (r: 0.478, p < 0.004). There was a marked difference in survival between patients with MM with Ki-67 greater than 8% and patients with Ki-67 less than 8%, in favor of the latter (p < 0.07). We conclude that Ki-67 determination during routine pathological analysis of bone marrow in newly diagnosed MM could provide useful information about the proliferative activity and prognosis of the disease.     

Pegylated liposomal doxorubicin hydrochloride (PLD) and paclitaxel in recurrent or metastatic head and neck carcinoma: a phase I/II study conducted by the Hellenic Cooperative Oncology Group (HeCOG)

A phase I pharmacokinetics and dose-finding study and a phase II study of the combination of pegylated liposomal doxorubicin HCl (PLD) and paclitaxel were conducted in patients with recurrent or metastatic head and neck cancer (HNC). Sixty patients with recurrent or metastatic disease were enrolled in the study: 11 patients in the phase I study and 49 patients in the phase II study. In the phase I study, the initial dose level of PLD was 35 mg/m as a 1-h infusion with escalating increments of 5 mg/m until the maximum tolerated dose (MTD) was reached. A fixed dose of paclitaxel (175 mg/m) was administered as a 3-h infusion. The combination was administered every 28 days. Pharmacokinetic studies performed on 10 patients indicated that the sequence of drug administration did not cause clinically significant modifications in the pharmacokinetics of either drug. The MTD for PLD was 45 mg/m (dose level 3) and the dose-limiting toxicity was febrile neutropenia, occurring in three of five patients. The phase II dose of PLD was 40 mg/m (dose level 2) and a total of 214 cycles were delivered. Grade 3 or 4 neutropenia was observed in 26% patients and febrile neutropenia occurred in 16% of patients. Grade 3 palmar-plantar erythrodysesthesia (PPE) was recorded in only one patient. The overall response rate was 28% for patients with non-nasopharyngeal tumors [95% confidence interval (CI) 15-45%] and 28.6% for the study population (95% CI 17-43%). The median survival for the study population was 9.7 months; 1-year survival was 38%. We conclude that the recommended dose for the combination of PLD and paclitaxel is 40 and 175 mg/m every 28 days, without granulocyte colony stimulating factor support. The combination of paclitaxel with PLD demonstrated activity in recurrent or metastatic HNC, a favorable toxicity profile and relative ease of administration.     

Retrospective study of febrile seizures: subsequent electroencephalogram findings,unprovoked seizures and epilepsy in adolescents

A retrospective questionnaire to determine the prevalence of febrile seizures was given to adolescents (16- and 17-year-olds) in the final 2 years of secondary school at the five schools in Alexandroupolis, Greece. Parents were interviewed, and clinical and electroencephalographic examinations were performed in all adolescents with a history of febrile seizures. Of 1708 adolescents, 56 (3.3%) had experienced at least one febrile seizure. Of these, 44 (78.6%) were simple and 12 (21.4%) were complex febrile seizures. Recurrent seizures occurred in 22 cases (39.3%), and the mean age at onset was 25.1 months. There was a positive first-degree family history in eight cases (14.3%) and this increased to 27.3% in cases with recurrent seizures. Two of the adolescents (3.6%) had had one unprovoked seizure before the age of 3 years, and another two children developed epilepsy. Epileptiform electroencephalogram discharges were observed in only one case (1.8%) with generalized tonic-clonic epilepsy.     

Dose-dense sequential adjuvant chemotherapy with epirubicin, paclitaxel and CMF in high-risk breast cancer

Dose-dense sequential chemotherapy appears to be a promising approach in the management of patients with operable breast cancer. We evaluated the tolerability of such a novel chemotherapeutic regimen in high-risk patients. From February 1995 until September 1997, 49 women with histologically confirmed breast cancer and > or =10 involved axillary nodes were treated postoperatively with three cycles of epirubicin (110 mg/m(2)) followed by three cycles of paclitaxel (250 mg/m(2) in a 3-hour infusion) followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m(2), methotrexate 57 mg/m(2), fluorouracil 840 mg/m(2); E-T-CMF). All cycles were repeated every 2 weeks with G-CSF support. Ovarian ablation with monthly injections of triptorelin for 1 year was performed in premenopausal patients and tamoxifen was prescribed for 5 years to all women with positive receptor status after the completion of chemotherapy. A total of 456 cycles of chemotherapy were administered, 363 (80%) of them at full dose. Forty-seven (96%) patients received all 9 cycles of chemotherapy. Relative dose intensity of epirubicin was 0.98, of paclitaxel 0.97, of cyclophosphamide 0.99, of methotrexate 0.98 and of fluorouracil 0.99. Grade 3--4 toxicities included anemia (8%), leukopenia (8%), peripheral neuropathy (6%), neutropenia (4%), thrombocytopenia (4%), stomatitis (2%), diarrhea (2%), fatigue (2%) and hypersensitivity reaction (2%). Febrile neutropenia occurred in 2 patients. Alopecia was universal. After a median follow-up of 3 years, 11 women (22%) relapsed and 4 (8%) died. The 3-year actuarial disease-free survival rate was 72% and the 3-year overall survival rate 90%. The E-T-CMF regimen is well tolerated, as adjuvant treatment, in patients with operable breast cancer with promising activity and deserves further evaluation in phase III studies.     

Treatment of pancreatic cancer with a combination of docetaxel, gemcitabine and granulocyte colony-stimulating factor: A phase II study of the Greek Cooperative Group for Pancreatic Cancer

Purpose:To evaluate the tolerance and efficacy of front-linedocetaxel plus gemcitabine treatment in patients with inoperable pancreaticcancer. Patients and methods:Fifty-four patients with locally advancedor metastatic pancreatic cancer were enrolled. Gemcitabine (1000mg/m²) was administered on days 1 and 8 and docetaxel (100mg/m²) on day 8, every three weeks; rh-G-CSF (150ìg/m² s.c.) was given prophylactically on days9–15. Results: Seven (13%) patients achieved partial response and18 (33%) stable disease (intent-to-treat). The median duration ofresponse was 24 weeks, time to tumour progression 32 weeks, and overallsurvival 26 weeks. Performance status was improved in 33% of patients,pain in 43%, asthenia in 16%, weight gain in 28% andappetite in 27%. Grade 3–4 neutropenia occurred in 17(31%)patients and grade 3–4 thrombocytopenia in four (4%). Six(11%) patients developed febrile neutropenia and one of them died fromsepsis. Conclusions:This combination is a relatively well-toleratedout-patient regimen for patients with inoperable pancreatic cancer.     

Coronary CTA assessment of coronary anomalies

Coronary anomalies occur in <1% of the general population and can range from a benign incidental finding to the cause of sudden cardiac death. The coronary anomalies are classified here according to the traditional grouping into those of origin and course, intrinsic arterial anatomy, and termination. Classic coronary anomalies of origin and course include those in which a coronary artery originates from the contralateral aortic sinus or the pulmonary artery with anomalous course. Single coronary artery anomalies, in which single coronary artery branches to supply the entire coronary tree, are also included in this category. Anomalies of intrinsic arterial anatomy are a broad class that includes myocardial bridges, coronary ectasia and aneurysms, subendocardial coursing arteries, and coronary artery duplication. Coronary anomalies of termination are those in which a coronary artery terminates in a fistulous connection to a great vessel or cardiac chamber. In the case of those anomalies associated with a risk of sudden cardiac death, the relevant imaging features on CT angiography (CTA) associated with poorer prognosis are reviewed. Recent guidelines and appropriateness criteria favor the use of coronary CTA for the evaluation of coronary anomalies. Although invasive angiography has historically been used to diagnose coronary anomalies, multidetector CT imaging techniques have now become an accurate noninvasive alternative. Cardiac CTA provides excellent spatial and temporal resolution, allowing accurate anatomical assessment of these anomalies.     

Irinotecan combined with docetaxel in pre-treated metastatic breast cancer patients: a phase II study

Purpose: This is a phase II study where a novel chemotherapy combination was tested in pre-treated breast cancer patients: docetaxel and irinotecan have already been established as agents for breast and colorectal cancer, respectively. Methods: Forty-eight (median age 54 years, range 26–77 year) patients, all evaluable, were enrolled. All patients had been pre-treated with anthracycline-combined chemotherapy, 30 of whom were also treated with paclitaxel and 2 with docetaxel. World Health Organization (WHO) performance status was 0–2. The dominant metastasis was in the liver (54.17%), in the lungs (27.08%), in soft tissues (12.50%) and in the skeleton (6.25%). Treatment involved irinotecan infusion 200 mg/m² for 90 min and docetaxel infusion 80 mg/m² for 90 min, repeated once every 3 weeks. Results: Twenty-five (52.08%, 95% confidence interval [CI] 37.95–66.21) patients showed responses: 3 complete (6.25%, 95% CI 0–13.05) and 22 (45.83%, 95% CI 31.74–59.92) partial; the most responsive metastases were observed at the liver site (53.85%). Grade 3 and 4 neutropenia was observed in 18 patients (37.50%); 14 (29.17%) patients developed anaemia and three (6.25%), thrombocytopenia. Concerning non-haematologic toxicity, alopecia and fatigue were common; grade 3 diarrhea was observed in only one (2.08%) patient. Conclusion: The irinotecan-docetaxel combination produces quite a high response rate in pre-treated advanced breast cancer patients.     

Nephrobronchial fistula. Case report

A 26-year-old woman presented with a six-year history of right staghorn calculus and pyonephrosis. Intravenous pyelography showed a non-functioning right kidney and chest radiography, an elevated right hemidiaphragm and fluid in the right costaphrenic space. At operation a nephrobronchial fistula was found, and nephrectomy and subdiaphragmatic drainage of the lung abscess was carried out. Culture of the pus grew Proteus mirabilis. The patient made an uneventful recovery and was discharged on the sixteenth day after operation.