Combination cisplatin-vinorelbine for relapsed and chemotherapy-pretreated metastatic breast cancer.

The purpose of this study was to evaluate the combination of cisplatin and vinorelbine (PVn) for relapsed and chemotherapy-pretreated metastatic breast cancer. Twenty-three patients with metastatic breast cancer and prior chemotherapy were entered in a phase II study between June 1993 and December 1994. Eleven patients were premenopausal and 12 were postmenopausal. Follow-up data up to June 1997 are presented. All patients received cisplatin at a dose of 90 mg/m2 divided over 3 days as 30 mg/m2 infused over 4 hours. Intravenous vinorelbine 25 mg/m2 was given on days 1 and 8 or 15 according to patients' blood counts. Cycles were given every 3 to 4 weeks. An overall response rate of 61% (16/23 patients) was observed. Complete remission was obtained in six patients (26%) and partial remission was obtained in nine patients (35%). The duration of response ranged from 3 to 9 months, with an average of 4 months. Stable disease was noted in 29.1% and progressive disease in 8.3%. Overall survival at 12 months was 50%, and at 36 months it was 8%. Five of 12 patients (42%) who had prior doxorubicin therapy responded well to cisplatin-vinorelbine. Of those 12, seven were refractory and progressive on a doxorubicin-containing regimen, one had complete remission, and four had partial remission. Hematologic toxicity was acceptable. Treatment was delayed because of neutropenia in nine cycles (9.2%) and grade 2 leukopenia occurred in 54% of cycles. Febrile neutropenia occurred in seven cycles (7.1%), and five cycles were complicated by documented sepsis (5.1%). No treatment-related mortality occurred. Thrombocytopenia (grade 3) was seen in 27% of cycles, with no patient having a platelet count below 50,000 or bleeding episodes. Other toxicities were not major or dose-limiting. In conclusion, the combination of cisplatin and vinorelbine produced good responses: 61% response rate (16 of 23 patients) in relapsed, refractory, and heavily pretreated metastatic breast cancer, with 50% survival at 1 year, 12% at 2 years, and 8% at 3 years. In addition, a response rate of 42% (5 of 12 patients) was seen in patients resistant to anthracyclines.

Cancer in Lebanon: analysis of 10,220 cases from the American University of Beirut Medical Center.

Cancers seen and recorded between 1983 and 1995 in the Hospital Tumor Registry at the American University of Beirut Medical Center (AUBMC), one of the largest primary and tertiary care hospitals in Lebanon, were retrospectively reviewed and analyzed. There was a total of 10,220 cases, excluding 916 skin cancers other than skin melanoma, averaging 786 cases per year. There were 5086 cancer cases in males with the five most common cancers being: lung cancer (915 cases: 17.9%) followed by bladder cancer (503 cases: 9.8%), larynx (438 cases: 8.6%), lymphoma (393 cases: 7.7%) and leukemia (336 cases: 6.6%). As for female cancer cases, a total of 5134 cases were observed with the five most common cancers being: breast cancer (1821 cases), followed by cervical cancer (535 cases), colo-rectal cancer (256 cases: 4.9%), lymphoma (232 cases: 4.5%), and brain cancer (213 cases: 4.1%). The average age for all cancer cases was 50.5 years with a standard deviation (SD) of 18.8 years. The average age of females (48.8 yrs; SD 17.4) was relatively lower than that of males (52.2 yrs; SD 19.9) and the difference was statistically significant. 40.6% of the patients were under the age of 50 years. 49% of breast cancer patients were below 50 years of age. In children less than 15 years of age, there were 555 cases, with leukemia being the commonest (185 cases: 33.3% of childhood cases) followed by brain cancer (112 cases: 20.1%), lymphoma (63 cases: 11.3%), bone cancer (41 cases: 7.3%), soft tissue sarcoma (35 cases: 6.3%) and kidney cancer (28 cases: 5.0%). Lung cancer in males and breast cancer in females are the most common cancers in Lebanon. These cancers are amenable to prevention (cigarette cessation and anti-smoking campaigns for lung cancer) and early detection (screening, regular breast examination and mammography for breast cancer). Our paper emphasizes the importance of addressing those and other issues including bladder cancer and age at diagnosis of breast cancer. It also presents important epidemiological and historical reference data on cancer in Lebanon during the civil war and immediately after it.

Cancer in Lebanon: an epidemiological review of the American University of Beirut Medical Center Tumor Registry (1983-1994).

PURPOSE: Cancers recorded in the Tumor Registry at the American University of Beirut Medical Center (AUBMC), the largest tertiary care center, in Lebanon were reviewed. METHODS: Results were compared with those from the same center 30 years ago and current data from western Asia. RESULTS: Between 1983 and 1994, 9364 cases were recorded, averaging 780 cases per year, representing more than one-third of the national case-load. Cases were almost equally distributed between males and females. Average age of females was significantly younger (48.7 years) than that of males (52.2 years). Among males, the five most frequently reported cancers were of the lung, bladder, larynx, lymphoma, and leukemia. Among females, the four most frequently reported cancers were of the breast, cervix uteri, lymphoma, and brain, with leukemia and corpus uteri ranking equally as fifth. Over the past 30 years, the frequency of colorectal cancer decreased and that of lung cancer increased in both sexes. Oral cancer decreased dramatically among males. Digestive system cancers in this series were less frequent than in cumulative data from western Asia area. CONCLUSIONS: Cancer dynamics changed little since the 1950s, except regard to cancers related to smoking and diet. Diet differences may explain the lower frequencies of digestive cancers in Lebanon as compared with elsewhere in western Asia. The potential impact of cancer prevention and early detection on highly prevalent cancer types such as lung, larynx, breast, and cervix was highlighted.

Pressure ulcer accelerated healing with local injections of granulocyte macrophage-colony stimulating factor.

This is the first report of granulocyte macrophage-colony stimulating factor (GM-CSF) inducing accelerated healing of a sacral pressure ulcer in a bedridden patient with bilateral hemiplegia. GM-CSF was diluted and injected locally around and into the ulcer bed every 2-3 days for 2 weeks, then weekly for 4 weeks until complete healing occurred. A new firm granulation tissue was noted within a few days. The ulcer showed 85% healing within 2 weeks and 100% by 2 months. Healing started from the periphery and from within the ulcer bed at sites of GM-CSF injections. It was slower at areas where there was complete necrosis and detachment of skin from underlying tissue. The ulcer remained closed until the patient's sudden death 9 months later. A biopsy of granulation tissue showed inflammatory cells and reactive fibroblasts. The potential role of GM-CSF and growth factors in pressure ulcer therapy and wound healing are discussed.

Increased aminoglycoside dosage requirements in hematologic malignancy.

Aminoglycoside pharmacokinetic parameters were studied prospectively in 27 patients with an underlying hematologic malignancy and fever associated with neutropenia and in 18 control patients. Pharmacokinetic parameters and dosages were determined by linear regression analysis of a one-compartment model by the method of Sawchuk et al. (R. J. Sawchuk, D. E. Zaske, R. J. Cippolle, W. A. Wargin, and R. G. Strate, Clin. Pharmacol. Ther. 21:362-369, 1976). Significant differences between the study and control groups were found for aminoglycoside volume of distribution (0.40 +/- 0.1 versus 0.27 +/- 0.05 liter/kg [mean +/- standard deviation], respectively; P less than 0.0001), clearance (116.6 +/- 48.9 versus 68.6 +/- 26.7 ml/min, respectively; P less than 0.0001), half-life (2.27 +/- 0.66 versus 3.5 +/- 1.8 h, respectively; P less than 0.0001), and elimination rate constant (0.33 +/- 0.11 versus 0.24 +/- 0.09 h-1, respectively; P less than 0.001). The percentage of bone marrow blast cells (at the time of diagnosis) in patients with acute leukemia significantly correlated with increased aminoglycoside clearance (R2 = 36.98%; P = 0.0001). Patients with stage IV lymphomas (Hodgkins disease and non-Hodgkins lymphoma) had a significantly increased clearance compared with patients with lower stages of lymphomas (105.1 +/- 18.5 versus 84.1 +/- 14.9 ml/min; P = 0.014). Fever, leukocyte count, or chemotherapy, among other clinical and laboratory parameters that were studied, had no significant correlation or effect on aminoglycoside disposition. The average dose of amikacin required to maintain peak concentrations in serum above 20 micrograms/ml in patients with a hematologic malignancy was 27.5 +/- 8.43 mg/kg per day. Pharmacokinetic parameters and dosages for the control patients were comparable to general literature standards. we conclude that the dosages recommended by the manufacturers or those derived from nomograms underestimate the aminoglycoside volume of distribution and clearance in patients with a hematologic malignancy and result in suboptimal peak aminoglycoside concentrations in serum. We recommend that in febrile neutropenic patients with an underlying hematologic malignancy, amikacin be initiated at 7.5 to 10 mg/kg per dose every 8 h (2 to 2.5 mg/kg per dose every 8 h for gentamicin) and adjusted within 24 h based on individual pharmacokinetic analysis.

Infectious complications during therapy of acute leukaemia in Saudi Arabia.

In 40 febrile neutropenic episodes during the induction and consolidation chemotherapy of acute leukaemia in Riyadh, 51% of organisms causing septicaemia were gram-negative, 26% gram-positive, 8% anaerobes and 15% fungi. In 21 (52%) febrile episodes there were pulmonary infiltrates; of the 12 where aetiology was known, six were due to fungi. Pulmonary infiltrates progressed to adult respiratory distress syndrome and death in nine instances. There was no significant occurrence of parasitic and tropical infections. The results show that the pattern of infection, during therapy of acute leukaemia in developing countries, may have important differences when compared with western centres. Empiric amphotericin B may need to be introduced at an earlier stage in patients with persistent fever or progressive pulmonary infiltrates.

Cavitating pneumonia due to Trichosporon beigelii in a patient with acute myeloid leukaemia.

A 21-year-old man with acute myeloid leukaemia developed cavitating pneumonia while neutropenic and on broad spectrum antibiotics following induction chemotherapy. Trichosporon beigelii was isolated from several samples of sputum. He was successfully treated with amphotericin B. Previous reports of lung infection with this organism are reviewed.

Combination chemotherapy for primary small intestinal lymphoma in the Middle East.

Twelve patients with primary small intestinal lymphoma were followed prospectively for 3 years. Endoscopic abnormalities were diagnostic of lymphoma in all cases where the duodenum was involved (83%). In three cases (25%) the disease extended to the stomach. One patient (8%) had diffuse small cell cleaved and 11 (92%) diffuse large cell lymphoma stages I (8%), II (25%), III (58%) and IV (8%). Nine of them were unresectable and primarily treated with combination chemotherapy; 67% achieved complete remission, 22% partial response and 11% no response. Only one patient relapsed and achieved a second remission. All complete remission patients are currently alive and free of disease at a median follow-up of 36 months. Overall survival for all patients is 58%, and disease-free survival is 50%. No instance of chemotherapy-related bleeding or perforation was seen. Tetracycline was necessary for the treatment of IPSID-associated diarrhea and malabsorption in spite of cytotoxic chemotherapy.

Direct spread of medulloblastoma in adjacent extrameningeal tissues.

A case of a medulloblastoma with extensive intradural dissemination and direct tumour spread from a lumbosacral deposit in the pelvis is presented. A review of the literature revealed six similar cases. In all of them direct invasion of contiguous structures occurred at sites of secondary deposits. Two predilection site were identified: 1. The anterior fossa with tumour invasion of the paranasal air sinuses. 2. The lumbosacral spine with tumour extension into the retroperitoneum and pelvis. Generally, this unusual mode of tumour spread indicates a final stage in the course of the disease. The possible pathogenesis is discussed.

Treatment of acquired amegakaryocytic thrombocytopenic purpura with cyclophosphamide.

A patient with severe amegakaryocytic thrombocytopenic purpura was treated with cyclophosphamide and had an excellent response after four weeks. His condition remained in complete remission for at least five months. Acquired amegakaryocytic thrombocytopenic purpura is a rare disorder with several possible causes. An intrinsic defect at the level of the megakaryocyte colony-forming units, or a circulating autoantibody directed against these colony-forming units has been suggested. This patient's response to cyclophosphamide supports the hypothesis of an immune mechanism in some of these cases, and it is recommended that immunosuppressive therapy be further evaluated.

Hepatotoxicity following vincristine therapy.

A patient is reported with small cell lung cancer treated with combination chemotherapy (cyclophosphamide, vincristine and etoposide [VP-16-213] who developed transient liver function abnormalities secondary to vincristine therapy. Serum transaminase (SGOT and SGPT) levels rose by 2 to 6 times, lactic dehydrogenase (LDH) 1.5 to 2 times, and alkaline phosphatase and gamma-glutamyl transpeptidase (GGTP) 1.5 to 2 times normal. Enzyme abnormalities were observed by the 6th day following drug administration and returned to normal between 16 and 48 days, except for the GGTP elevations which persisted longer. Vincristine has been suspected to cause liver damage and to enhance radiation-induced hepatic injury. The authors report this case of moderate transient transaminitis confirmed by rechallenge with vincristine.