In two sequential trials, 154 patients were treated with dosages of ifosfamide, ranging between 8 and 18 g/m2divided over 4 days, with mesna uroprotection. The first was a phase II efficacy trial in 125 advanced sarcoma patients (Antman et al: J Clin Oncol 7:126-131, 1989), while the second was a dose escalation trial involving 29 patients (Elias et al: J Clin Oncol 8:170-178, 1990). In the first trial, patients received 8 to 10 g/m2ifosfamide either by bolus or continuous infusion. The response rate for the 64 patients receiving bolus administration was 23% compared with 12% for the 60 patients receiving a continuous infusion schedule (P = .09). Of the 154 patients, 144 had sarcoma and had failed at least one previous regimen. Of these 144, 4% responded completely and 23% had a complete or partial response. The maximum tolerated dose of ifosfamide was 16 g/m2in the second trial. Dose-limiting renal toxicity was observed at 18 g/m2ifosfamide (Elias et al: J Clin Oncol 8:170-178, 1990). The duration of myelosuppression and the frequency and severity of mucositis and renal tubular acidosis were dosedependent. A median of 11 days (range, 8 to 18) of granulocytopenia (<500/μL) were observed. Thus, autologous bone marrow reinfusion was not required. Severe central nervous system toxicity (transient confusion, hallucinations, and somnolence) was observed sporadically at both low- and high-dose levels. The first four patients on the standard-dose study did not receive mesna because it was unavailable; three developed gross hematuria. In patients who received mesna, hematuria was uncommon. Hematuria in the group as a whole was significantly associated with a lack of uroprotection, but was not associated with prior cyclophosphamide, pelvic radiotherapy, age, or bolus versus a continuous infusion schedule. Patients receiving ifosfamide with mesna uroprotection can tolerate considerable dose escalation over the usual prescribed doses before nonhematologic toxicity becomes d...
Bell, DA & Zhang, C 1990, 'Description and Treatment of Deadlocks in the Hecodes Distributed Expert System', IEEE Transactions on Systems, Man and Cybernetics, vol. 20, no. 3, pp. 654-664.
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The causes of deadlocks in distributed expert systems are examined, classified, and methods of processing them are put forward. In particular, this problem is discussed within the framework of a working prototype distributed expert system, Hecodes. The effect of the proposed deadlock resolution methods is discussed. © 1990 IEEE
Cnaan, A & Ryan, L 1990, 'Survival analysis in natural history studies of disease (I: Reply)', Statistics in Medicine, vol. 9, no. 10, p. 1222.
Elias, A, Ryan, L, Aisner, J & Antman, KH 1990, 'Mesna, doxorubicin, ifosfamide, dacarbazine (MAID) regimen for adults with advanced sarcoma', Seminars in Oncology, vol. 17, no. 2 SUPPL. 4, pp. 41-49.
The mesna, doxorubicin, ifosfamide, dacarbazine regimen produced a 47% response rate (including 10% complete responses) in 105 eligible adults with advanced sarcoma. The major dose-limiting toxicity was granulocytopenia. There was one toxic death from sepsis. Central nervous system and renal toxicity occurred infrequently, perhaps as a result of the continuous-infusion schedule. This regimen is being evaluated further in advanced disease, the adjuvant setting, and in combination with bone marrow colony-stimulating factors. © 1990.
Goetghebeur, E & Ryan, LM 1990, 'A modified log rank test for competing risks with missing failure type', Biometrika, vol. 77, no. 1, pp. 207-211.
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We propose a modified log rank test for the analysis of competing risks survival data, when failure type is missing for some individuals. The proposed test reduces to a standard log rank test when all failure types are known. The test arises from a partial likelihood, constructed under semiparametric assumptions on the relationship between cause-specific hazards.
Keiding, N, Knuiman, MW, Cnaan, A & Ryan, L 1990, 'Letter to the editor survival analysis in natural history studies of disease', Statistics in Medicine, vol. 9, no. 10, pp. 1221-1222.
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ANTMAN, KH, ELIAS, A & RYAN, L 1989, 'IFOSFAMIDE AND MESNA - RESPONSE AND TOXICITY AT STANDARD-DOSE AND HIGH-DOSE SCHEDULES', SEMINARS IN ONCOLOGY, SYMP ON ADVANCES IN IFOSFAMIDE CHEMOTHERAPY, W B SAUNDERS CO, KEY BISCAYNE, FL, pp. 68-73.
ELIAS, A, RYAN, L, AISNER, J & ANTMAN, KH 1989, 'MESNA, DOXORUBICIN, IFOSFAMIDE, DACARBAZINE (MAID) REGIMEN FOR ADULTS WITH ADVANCED SARCOMA', SEMINARS IN ONCOLOGY, SYMP ON ADVANCES IN IFOSFAMIDE CHEMOTHERAPY, W B SAUNDERS CO, KEY BISCAYNE, FL, pp. 41-49.