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The charts of 273 cancer patients were retrospectively analyzed in order (1) to evaluate the frequency of opioid change (OCH) when adjuvants (antiemetics/laxatives) were administered on a regular basis and co-analgesic medication as indicated by the specific type of pain, (2) to define risk factors for the request of OCH, and (3) to reveal settings in which OCH may not be recommended as a first-line therapeutic intervention. Opioids used included morphine, fentanyl, 1-methadone, and buprenorphine. Out of 273 patients, 103 changed opioids at least once, with a success rate of 65%. The indications for the OCH were insufficient analgesia in 43%, intolerable side effects in 20%, both in 15%, and other reasons in 22% of patients. The frequency of OCH was not influenced by the routine use of adjuvants or co-analgesics except corticosteroids, which raises queries about the concept of an opioid-sparing effect of co-analgesics. The occurrence of intolerable side effects is thought not to be dose dependent so much as to reflect differences in the individual tolerability of a distinct opioid for whatever reason (genetically fixed or individually acquired pharmacodynamic or kinetic properties). Moreover, there was strong evidence for the existence of an unpredictable and incomplete cross-tolerance between opioids, which meant careful titration of the new opioid was required after OCH. The overall frequency of OCH was similar to that observed in previous studies in spite of the documented addition of adjuvants and co-analgesics. This retrospective study supports the notion that opioid rotation must be retained as an essential therapeutic option even with optimized adjuvant and co-analgesic regimens.

The objective of this study was to investigate the prognostic impact of the reduction of Philadelphia chromosome (Ph) positive metaphases by treatment of chronic myelogenous leukaemia (CML) with interferon (IFN) alpha. Therefore, we evaluated the outcome of patients with previously untreated chronic phase Ph-positive CML, enrolled from 1984 to 1990 into two consecutive IFN trials at our institution. Of a total of 71 patients, 62 (87%) were evaluable for cytogenetic response. No cytogenetic improvement was seen in 16 patients (23%), 28 patients (38%) had a decrease in Ph-positive bone marrow metaphases to levels ranging from 35% to 95%, and nine patients (13%) to levels between 5% and 34%. In nine patients (13%), Ph-positive metaphases were no longer detectable. After a median follow-up period of 33 months, the projected 5-year survival is 55% for the 62 patients evaluable for cytogenetic response. In this patient population there was no significant difference in the survival probability according to patients' risk status as defined by the Sokal score. Categorization according to the extent of Ph reduction, however, allowed three groups with significantly different prognoses to be identified. Patients achieving a Ph reduction to less than 35% were found to constitute a low risk group with a median survival not yet known and a projected 5-year survival of 90%. The 5-year survival rate was 55% for patients with a Ph reduction to levels between 35% and 95%, and less than 10% for those without any cytogenetic improvement. Thus, this study demonstrates that cytogenetic improvement on IFN treatment is an important prognostic factor for survival.

To assess the influence of pretransplant cytoreductive therapy with special reference to interferon-alpha (IFN-alpha) treatment on major endpoints of allogeneic bone marrow transplantation (BMT), we studied 133 consecutive patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) in first chronic phase who received marrow grafts from HLA-identical family (n = 103) or alternative donors (n = 30) at a referral-based transplant center. Fifty of these patients (38%) were previously exposed to IFN-alpha for a median duration of 14 months (range, 1 to 61 months), whereas 83 patients (62%) exclusively received hydroxyurea and/or busulfan therapy between 1 and 129 months (median, 15 months) pretransplant. Using the categorized treatment duration with each pretransplant cytoreductive agent as a measure for individual patient exposure to each agent, prolonged ( > 12 months) IFN-alpha administration was identified as the sole significant pretransplant therapy-related predictor of transplant outcome by proportional hazards regression analysis. The adjusted risk ratio (RR) of transplant-related mortality (TRM) was 2.5-fold higher (95% confidence limits [95% CL], 1.4 to 4.5; P < .004) compared with other pretransplant therapy and this was mainly attributable to a 3.1-fold higher RR (95% CL, 1.4 to 6.4; P < .005) of fatal posttransplant infections after prolonged IFN-alpha treatment pretransplant. Marrow graft failure developed exclusively among 7 of 30 patients (23%) with donors other than HLA-identical family members and was further restricted to patients who had been previously exposed to IFN-alpha. The probability of graft failure was 49% +/- 28% in 17 patients pretreated with IFN-alpha compared with 0% for the other 13 patients with mismatched family or unrelated donors (P < .008). In addition, a significant delay in neutrophil and platelet count reconstitution was observed among patients with donors other than HLA-identical family members after pretransplant IFN-alpha exposure. No influence of pretransplant cytoreductive therapy on either acute and chronic graft-versus-host disease or leukemic relapse was detected in this study. As a consequence of its adverse effect on TRM, prolonged pretransplant IFN-alpha treatment was independently associated with a 2.5-fold lower likelihood (95% CL, 1.4 to 4.5; P < .003) of 5-year overall survival and with a 2.3-fold lower likelihood (95% CL, 1.3 to 4.2; P < .004) of 5-year disease-free survival postransplant after adjustment for other significant prognostic factors in multivariate analysis.(ABSTRACT TRUNCATED AT 400 WORDS)