No abstract

Ifosfamide (IFS) is a new alkylating oxazaphosphorine related to cyclophosphamide. Various side effects have been reported; however, cardiotoxicity is not known to occur in humans. We report for first time acute cardiac side effects upon IFS treatment in the form of supraventricular arrhythmias and ST-T wave changes. IFS dose ranged from 6.5 g/m2 to 10 g/m2 fractionated in 3 or 5 days and infused i.v. over 4 h daily together with 2-mercaptoethane sulphonate sodium (Mesna). Arrhythmias appeared to be reversible upon discontinuation of the drug. In one patient, readministration of IFS led to arrhythmia that was refractory to treatment. Factors predisposing to the development of cardiac side effects could not be determined in this study. We suggest that patients who receive IFS treatment should be monitored for the occurrence of cardiac abnormalities. Readministration of the drug may be contraindicated in such patients.

Diarrhea is a well-recognized side effect of chemotherapy, which affects the quality of life and when refractory is potentially life threatening. Irinotecan (CPT-11) is associated with an elevated incidence of chemotherapy-induced diarrhea and subsequent morbidity. Standard antidiarrheal treatment is based on high-dose loperamide, but this agent is associated with a significant failure rate. Octreotide is active against chemotherapy-induced diarrhea caused by fluoropyrimidines and irinotecan, with a distinct mechanism of action. We administered octreotide in a phase I trial in 37 patients who received irinotecan and experienced loperamide-refractory diarrhea, 23 of whom experienced grade III-IV diarrhea and were treated with loperamide. The 13 patients in whom to loperamide failed to control diarrhea received octreotide, with a high response rate (92%). We conclude that octreotide is effective against loperamide-refractory diarrhea resulting from irinotecan-based chemotherapy.

Purpose: The aim of this study is to compare various time schedules of granulocyte colony-stimulating factor (G-CSF) treatment in a clinical model of patients who received high-dose cyclophosphamide (HDCY 45 g/m²) for the treatment of an underlying malignancy in order to investigate the optimal time (preemptive vs. supportive) of G-CSF initiation upon the incidence and duration of cytopenias and related parameters, such as incidence of febrile episodes, antibiotic use, duration and cost of G-CSF administration and overall clinical benefit and cost effectiveness of various schedules used. Patients and Methods: Seventy-two courses were given in a sequential cohort study. G-CSF was administered either 24, 48, 72, 96 h after chemotherapy (preemptive treatment) or upon the onset of leukopenia (WBC ≤1,000/µl) (supportive treatment). Study parameters were compared among the various groups as well as to a control group who received HDCY without G-CSF support. Results: (1) Patients who received G-CSF early (24, 48 h) had a shorter duration of leukopenia (WBC ≤1,000/µl) compared to those who received G-CSF at a later stage (72, 96 h) or as supportive treatment (p < 0.05). However the duration of neutropenia (ANC ≤500/µl) or thrombocytopenia (platelets ≤20,000/µl) was not affected by the different time schedules of treatment. (2) Patients who received G-CSF early (up to 72 h) had less febrile days with neutropenia in comparison to late treatment (>96 h), supportive and control groups (p < 0.05). The cost of antibiotics was also in favor of the early treatment group. The median duration of febrile days of the delayed (>72 h) treatment groups and antibiotic cost was similar to those in patients who did not receive G-CSF at all. (3) When G-CSF was given preemptively a shorter time was required to reach normal WBC (5,000/µl) in comparison to the sup- portive and control group. This was due to a prolonged WBC recovery rather than to an early onset of leukopenia (tail effect). A delayed leukopenia recovery occurs as administration of G-CSF is delayed. (4) As a result the required length of G-CSF treatment to reach normal WBC (5,000/µl) was shorter in the early treatment group and the cost from G-CSF use was less in that group in comparison to the late (>72 h) and supportive groups which indicated an increased cost without clinical benefit over controls. Conclusions: G-CSF administration after HDCY has a similar effect upon the incidence and duration of severe leukopenia and thrombocytopenia. However, severe leukopenia is shorter when G-CSF starts up to 72 h after HDCY. The length of G-CSF administration and its cost is also in favor of early initiation of treatment as well as the number of febrile days and antibiotic use. Delayed (>72 h) or supportive treatment indicate more febrile episodes, antibiotic use and higher cost when compared to the early groups. Late (>72 h) or supportive G-CSF administration in this study indicates no benefit versus no treatment in relation to length of leukopenia, febrile days, antibioti...

A phase II study of flutamide was conducted in 24 patients with stage III and IV ovarian cancer who failed chemotherapy and who had measurable disease. Flutamide was administered at a dose of 100 mg three times daily continuously until evidence of progression. Partial response observed in 1 of the 23 evaluable patients (4.3%) lasted 3 months. Two patients had stable disease (8.7%) for 7 and 8 months. The remaining 20 patients had progression of disease within 3 months. Toxicity was mild.