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Background: In febrile neutropenic patients, ceftriaxone plus an aminoglycoside is effective for the treatment of infection, while filgrastim reduces the extent and duration of neutropenia. Because the once daily dosing regimen of this combination permits ambulatory treatment, there is a need to test criteria for early hospital discharge., Methods: Hospitalized adult patients with febrile neutropenia (following chemotherapy) considered to be potentially treatable on a follow-up out-patient basis were entered into this open-label, multinational study. Patients received a once daily combination of ceftriaxone for > or =5 days, aminoglycoside for > or =2 days, and filgrastim until the absolute neutrophil count was > or =1.0x10(9)/l for 2 days. Those initially responding to therapy (reduction of fever by > or =1 degrees C within 72 h, and clinical improvement) were randomized into standard in-patient or follow-up out-patient treatment groups, the latter patients being discharged from hospital early, after meeting defined criteria., Results: 105 patients were enrolled, of whom 21 initial non-responders were not randomized. Efficacy was evaluable in 80 patients. Success (resolution of fever and symptoms, maintained for 7 days after cessation of therapy, and eradication of infecting pathogens) was similar among in-patients (40/42, 95%) and out-patients (34/38, 89%). The duration of hospitalization was shorter for out-patients than in-patients (median of 4 vs. 6 days, respectively). No hospital readmissions were necessary in out-patients. All other efficacy parameters assessed were comparable in both groups, as was tolerability/safety. One potentially drug-related death was reported., Conclusions: Patients who satisfy prospectively defined criteria for early discharge can be treated safely on an out-patient basis with a regimen of once daily ceftriaxone plus an aminoglycoside with filgrastim. In addition to reducing healthcare costs, it may improve patients' quality of life., (Copyright 1999 S. Karger AG, Basel.)

The aims of this study were to identify prognostic factors in patients (pts) with small cell lung cancer and to identify dominant prognostic factors independent of disease stage, to define prognostic subsets through recursive partitioning and amalgamation (RPA) and to analyze the clinical characteristics of long-term survivors. The prognostic significance of 27 pre-treatment variables was evaluated in 144 pts seen at a single institution. The current study confirmed the superior outcome for pts with limited disease (LD) in terms of response, response duration, time to treatment failure and survival when compared to those with extensive disease (ED). None of the variables independently predicted for response in patients with LD. Response correlated significantly with a good performance status (PS) for pts with ED and for the whole group. A good PS was the most significant predictor for prolonged survival in pts with LD. In ED a longer survival was associated with a normal pre-treatment albumin value, absence of weight loss and female gender. When the whole group was considered, PS and number of metastatic sites were identified as the most influential factors for survival independent of disease stage. RPA analysis defined 3 prognostic subsets based on stage of disease, PS and number of metastatic sites. The best survival rates were seen in pts with LD with a good PS and pts with ED, only one metastatic site and a good PS. 11% of pts survived > 2 years (18% LD, 6% ED). A complete response to chemotherapy was the most important predictor for long-term survival. Comparison of the data from this study with published results of protocol studies showed similar outcomes.

An analysis was performed on 127 consecutive women with advanced measurable ovarian cancer to evaluate factors predicting for survival. All patients received cis-platinum-based chemotherapy as treatment for stage IIIB to stage IV disease. Eighteen clinical, radiological, and biochemical parameters were subjected to univariate and multivariate analyses. Recursive partitioning and amalgamation (RPA) was used to define prognostic subsets with different survival potentials. In the univariate analysis, factors that predicted for survival were weight loss, histology, stage, number of metastases, presence of ascites, size of the residual tumor, and rate of tumor response. When these significant variables were included in a Cox model, advanced stage of disease, histology other than adenoserous carcinoma, the presence of tumor bulk, and a slow rate of tumor response independently predicted a poorer survival. Using the three disease-related prognostic variables, a RPA model was derived and three groups were identified with median survival times of 76, 28, and 21 months, respectively (P = 0.001). The best survival time of 76 months was seen in patients with stage III, nonbulky, adenoserous ovarian carcinoma. It is concluded that the rate of tumor response is important in predicting the outcome of patients with ovarian cancer. Furthermore, the interactions between prognostic factors are emphasized by the RPA model and a subgroup of patients with a projected 10-year survival of 50% is identified.

Background: Hormone-resistant prostate cancer can respond to mitomycin C or to suramin. This trial was undertaken to investigate the value of mitomycin C given with low dose suramin., Patients and Methods: Thirty-two patients with hormone-refractory prostate cancer were given suramin 350 mg/m2 daily for 5 days, followed by 350 mg/m2 weekly starting on day 14. Mitomycin C 12 mg/m2 was given every 5 weeks starting on day 14., Results: Toxicity included maculo-papular skin rash in 8 patients, haematological toxicity in 16 (anaemia 13, leucopenia 11 and thrombocytopenia 9, bleeding 8), infection in 4 and fatigue in 11. Ten patients developed neurotoxicity, (temporary sensory peripheral neuropathy in 8, upper limb motor neuropathy in 1, and restless legs syndrome in 1) and 9 developed proteinuria. Other toxicities were mild nausea and vomiting, oedema, transient elevation of liver enzymes, stomatitis, upper gastrointestinal symptoms, and alopecia. During induction treatment the median trough suramin level was 140 micrograms/ml (range 100-273) and during maintenance treatment the median suramin level was 93 micrograms/ml. The median overall trough level was 93 micrograms/ml. There were one complete and 6 partial responses. Fifteen patients had disease stabilization. The median time to treatment failure was 103 days, and the median survival 209 days., Conclusion: The combination of suramin and mitomycin C has therapeutic activity, but causes significant toxicity in patients with hormone-resistant prostatic carcinoma.

Background: Granisetron was shown to be a safe and effective antiemetic agent when given with initial cytostatic therapy. This study was undertaken to investigate the efficacy and safety of the continued use of granisetron., Methods: Ninety-one patients were given 438 cycles of granisetron during subsequent courses of cytostatic treatment. In 56 patients, 40 micrograms/kg i.v. was given in 159 cycles, and in 42 patients, 3 mg i.v. was given in 279 cycles. In patients having breakthrough symptoms, as many as two rescue doses were given to re-establish control., Results: Overall objective control of nausea and vomiting was observed in 88.6% of the 40 micrograms/kg-cycles and in 90.32% of the 3-mg cycles. In the 438 cycles given, complete control was achieved in 105 of 159 (66%) of the 40-micrograms/kg cycles and in 217 of 279 (77.78%) of the 3-mg cycles. Thirty-three patients received 97 cycles of cisplatin-based regimens. The objective control rate was 82.47% (80 of 97 cycles) in these patients. The control rate in patients receiving regimens not containing cisplatin was 94.4% (322 of 341 cycles). Rescue doses improved or resolved symptoms in 53 of 61 (86.9%) cycles. No statistically significant difference in nausea and vomiting control was seen between men and women or between the different age groups. The only toxicities encountered were headache in 14 of 438 (3.2%) cycles and mild constipation in 8 of 438 (1.8%) cycles., Conclusion: Granisetron is safe and well tolerated, maintains its antiemetic efficacy after repeated cycles of therapy, and is effective as an interventional treatment for nausea and vomiting.

Twenty one patients with hormone resistant prostate cancer were entered in a phase II study of pirarubicin 70 mg/m2, as a single intravenous injection given at 21 day intervals. All patients had leukopenia (9 severe or life threatening) and 2 died of septicemia. Thrombocytopenia occurred in 5 patients (one life threatening) and anemia in 12 patients. One partial response of 3 months duration was documented. Pirarubicin 70 mg/m2 given intravenously at 21 day intervals causes severe hematological toxicity and has minimal therapeutic activity in patients with hormone resistant prostate cancer.

A patient with a megakaryocytosis associated with a Philadelphia chromosome-positive chronic myeloid leukemia (CML) was found to have a trisomy of chromosome five. To our knowledge, this is the first case of trisomy 5 associated with a Ph + CML, particularly one with a megakaryocytosis. The trisomy 5 may be associated with the resistance to cytostatic drugs found in this patient.

A retrospective analysis of data concerning 86 patients with multiple myeloma was carried out in order to evaluate factors affecting survival. The overall median survival was 621 days. In a univariate analysis the following factors were significantly associated with poor survival: serum creatinine greater than or equal to 150 mmol/l, haemoglobin less than 11 g/dl and serum calcium values greater than 2.75 mmol/l; and Eastern Cooperative Oncology Group performance status 3-4. However, age, sex, Durie and Salmon staging, lytic lesions, serum immunoglobulin concentration, urine Bence Jones protein, percentage of plasma cells in the bone marrow, proteinuria, and type of chemotherapy given were not significantly associated with survival. A strong prediction of survival was found by grouping the serum creatinine and haemoglobin levels of patients at presentation.

Acute non-lymphatic leukaemia and myelodysplasia occur in a larger percentage of patients treated with dibromodulcitol (DBD) than in patients treated with other cytostatics. Sister chromatid exchanges (SCE) in the lymphocytes in peripheral blood as well as other haematological parameters were measured in women with breast cancer to investigate whether women who had previously been treated with DBD as a part of their treatment regime had an increased frequency of SCE or another haematological abnormality attributable to DBD. SCE levels were elevated in women treated with DBD as well as in those treated with other cytostatics compared to the untreated control group. All other haematological parameters were normal. There was no significant difference in the number of SCEs between the patients who received DBD and those treated with other cytostatics. The increased frequencies of SCE in the treated patients are attributable to various cytostatic agents, and there is no significant permanent increase in the frequency of SCE after exposure to DBD.

Twenty-one patients with multiple myeloma were treated with idarubicin 45 mg/m2 orally day 1 and prednisone 60 mg/m2 day 1-4 every three weeks. Moderate to severe gastrointestinal and hematopoietic toxicity were observed. Twelve of the twenty-one patients had relapsed on prior treatment. Of these, 2 patients responded. Two patients had primary resistant disease, neither responded. Seven patients had received no prior treatment, three responded. Idarubicin and prednisone have modest activity in refractory myeloma, with short duration of response and severe toxicity.

Infections can cause autoantibody production. The purpose of this study was to determine the prevalence of autoantibodies in patients with chronic mycobacterial infections. Sera from 41 leprosy patients and from 49 untreated and 73 treated tuberculosis (TB) patients were tested for the presence of rheumatoid factor, antinuclear factor, and several other autoantibodies. The rheumatoid factor, measured by the Rheuma Tec RF latex test, was positive in 2.4% of the leprosy patients and 2.7% of the treated TB patients but absent in the untreated TB group. The titers ranged from 40 to 160 international units. Positivity was dependent upon the technique utilized, and existed in 21% of untreated TB group and 4% of the treated TB patients when using the Rheuma-Wellcotest technique. The antinuclear antibody was positive in 7.3% of the leprosy group, 6.1% of the untreated TB group, and 15% of the treated TB patients (p = 0.0125). Antinuclear antibody positivity correlated with the duration of treatment of the TB patients (p = 0.025). The antinuclear antibody titers were low and gave no specific pattern on staining. No patient had antibodies against native deoxyribonucleic acid, ribonuclear protein, Ro (SS-A) or La (SS-B) antigens. Due to their low prevalence and frequency in these chronic infections, these autoantibodies should not lead to confusion in distinguishing these conditions from the connective tissue diseases.

A case of autoimmune thrombocytopenia associated with lung cancer is presented. The thrombocytopenia occurred 2 years before the diagnosis of lung cancer. Previous treatments include high doses of corticosteroids and splenectomy. The patient was managed with interferon, which resulted in an increase of the platelet count with control of the hemorrhagic manifestations with this syndrome.

Daytime plasma melatonin values were measured by radioimmune assay in 86 patients with breast cancer; 280 assays were done and compared with the clinical status of the patients. Patients in the advanced disease group had significantly higher levels than those in the adjuvant treatment group, and patients with progressive disease had significantly higher values than those in remission or with stable disease. No significant differences were found between different dominant metastatic disease sites. Multiple-regression tests showed a significant inverse correlation between survival and melatonin values.