A phase I/II study of the MDR modulator Valspodar (PSC 833) combined with daunorubicin and cytarabine in patients with relapsed and primary refractory acute myeloid leukemia.

The cyclosporine analog Valspodar (PSC 833, Novartis Pharma) is a strong inhibitor of the mdr1 gene product p-glycoprotein (pgp). A phase I/II study was conducted in order to evaluate if addition of Valspodar to treatment with daunorubicin and cytarabine, given to patients with primary refractory or relapsed acute myeloid leukemia, could increase the complete remission rate.Fifty-three patients were treated in cohorts of three to six patients. Twelve patients reached a complete remission in bone marrow, five of whom also normalized their peripheral blood values. Three patients experienced treatment-related deaths from pneumonia, liver failure and cerebral hemorrhage, respectively. It is concluded that Valspodar 10 mg/kg per 24 h in combination with daunorubicin 45 mg/m(2) for 3 days and cytarabine 1 g/m(2) twice daily for 4 days is tolerable in this heavily pre-treated group of patients. Due to the moderate treatment results, the phase II part of the study was ended prematurely. The modulation of only pgp did not give an obvious improvement of the treatment results in this group of patients.

The CARES-SF used for prospective assessment of health-related quality of life after stem cell transplantation.

OBJECTIVE: By employing the Cancer Rehabilitation and Evaluation System short form (CARES-SF) prospectively we wanted to focus on the rehabilitation needs after high-dose chemotherapy (HDC) and stem cell transplantation, in order to identify problems that should be addressed by health-care professionals during the course of disease and treatment. METHODS: The CARES-SF was administered before and at 2, 6 and 12 months post-transplant to 130 cancer patients treated with HDC and allogeneic (SCT) or autologous stem cell transplantation (ASCT). Physical function scale scores were compared with the corresponding scale of the EORTC QLQ-C30. RESULTS: The SCT group reported significantly better physical function than the ASCT group before transplant on both the CARES-SF (p<0.0001) and the EORTC QLQ-C30 (p<0.01). Almost identical mean CARES-SF scores across groups (SCT: 0.7-1.4, ASCT: 0.8-1.3) were found at the subsequent assessments, consistent with the QLQ-C30 data. Correlations between CARES-SF and QLQ-C30 Physical Function Scales ranged from 0.45 to 0.65. The SCT group had better psychosocial subscale scores (mean 0.4 and 0.5 versus ASCT: 0.7 and 0.8, p < 0.01) at the 6 and 12-month assessments, as well as better satisfaction on the marital subscale ( p=0.01) 6 months post-transplant. Few patients requested specific help: 19% at baseline with 'fear of the cancer progressing' and 9% with 'reduction in physical energy' after 6 and 12 months. CONCLUSION: The CARES-SF detected differences across groups of patients as well as within-patient changes over time. The possibility for patients to express their need for professional assistance renders the CARES-SF appropriate after SCT/ASCT. The sexual, marital and medical interaction subscales in particular address specific issues of relevance for follow-up care, compared with more traditional questionnaires assessing health related quality of life (HRQOL).