Advanced cervical cancer treatment in Harris County: pilot evaluation of factors that prevent optimal therapy.

OBJECTIVE: To document obstacles to completing outpatient treatment faced by indigent patients with cervical cancer and compare treatment costs. METHODS: A retrospective pilot case series study assessed all indigent Harris County residents referred from Lyndon Baines Johnson Hospital (LBJ) to The University of Texas M. D. Anderson Cancer Center (M. D. Anderson) for advanced cervical cancer treatment between February 2001 and April 2004. Twenty-seven patients required hospital admission during the expected course of outpatient treatment and were identified as the study group. Nine patients, drawn from the same cohort but able to successfully complete the expected course of treatment as outpatients, were selected as the control group. RESULTS: The median total treatment costs per patient in the study group (n = 27) was 28,892 US dollar more than the median treatment costs for the patients in the control group (n = 9) (P = 0.01). Median number of inpatient days in the study group was 19.6. Social factors identified as significantly different between the study and control groups included transportation difficulties (P = 0.006) and lack of social support (P = 0.08). Additional factors identified in the study group may have social significance such as accessible local housing (11% vs. 0%, P = 0.56) and noncompliance with treatment (37% vs. 11%, P = 0.22). CONCLUSION: A combination of the lack of adequate methods of transportation and social support may contribute to the high cost of treating indigent patients with cervical cancer in Harris County, Texas.

Effects of darbepoetin alfa administered every two weeks on hemoglobin and quality of life of patients receiving chemotherapy.

PURPOSE/OBJECTIVES: To review the effects on hemoglobin and quality of life of an every-two-week (Q2W) regimen of the erythropoietic agent darbepoetin alfa for treating patients with chemotherapy-induced anemia. DATA SOURCES: Published articles and abstracts. DATA SYNTHESIS: Darbepoetin alfa Q2W increases hemoglobin in patients with chemotherapy-associated anemia and is well tolerated. Increased hemoglobin is associated with improvements in fatigue and energy level. A starting dose of darbepoetin alfa 3.0 mcg/kg (approximately 200 mcg for an average 70 kg patient) Q2W produces a similar level of response to recombinant human erythropoietin. CONCLUSIONS: Darbepoetin alfa effectively treats chemotherapy associated anemia with fewer clinic visits and fewer injections than are required with conventional erythropoietic therapy. IMPLICATIONS FOR NURSING: The less-frequent dosing schedule of darbepoetin alfa can simplify anemia management for nurses and other clinic staff, and it offers patients greater freedom in their day-to-day activities, less dependence on caregivers, and less injection-associated discomfort.

Pilot study of Flt3 ligand comparing intraperitoneal with subcutaneous routes on hematologic and immunologic responses in patients with peritoneal carcinomatosis and mesotheliomas.

PURPOSE: This study compared the clinical toxicity and hematological effects of i.p. and s.c. administration of fms-like tyrosine kinase-3-ligand (Flt3-L; Amgen, Thousand Oaks, CA), a truncated glycoprotein that increases dendritic cells (DCs) and monocytes. EXPERIMENTAL DESIGN: Patients with peritoneal carcinomatosis or mesothelioma were randomly assigned to treatment with Flt3-L (25 micro g/kg, maximum 1500 micro g), i.p. or s.c., days 1-5 and 8-12, then changed to the alternative route at 4 weeks. Treatment was continued s.c. or i.p. at 8 weeks. RESULTS: Fifteen patients (14 evaluable) were randomized to receive i.p. (n = 8) or s.c. (n = 7) injections. Their median age was 55 years (range, 40-68 years). Primary tumors were as follows: ovarian/peritoneal cancer (n = 9); gastrointestinal cancer (n = 2); and mesothelioma (n = 4). Treatment was well tolerated without serious toxicity (24 i.p. cycles; 32 s.c. cycles). Treatment (i.p. or s.c.) resulted in significant increases in WBCs (WBC, monocytes, and Lin(-)DR(+) DCs), and platelets (during washout). Both interleukin (IL)-12(p70) and IL-10 were secreted by monocyte-derived DCs after in vitro exposure to maturation factors. Increased IL-12 versus IL-10 secretion responses and higher proportions of the CD11c(+) DC subset in post-Flt3-L specimens suggested a maturational shift toward the monocyte-derived DC phenotype had occurred. Three patients (2 with mesothelioma and 1 with gastrointestinal cancer) had stable disease for 8, 8, and 12+ months, respectively. CONCLUSIONS: Flt3-L, administered either i.p. or s.c., is well tolerated and produced similar increases in monocytes, DCs, and platelets. DCs from peripheral blood and peritoneal fluids showed cell surface phenotypic and cytokine maturational responses to activation stimuli. These findings suggested that Flt3-L, in combination with suitable activating agents, could be developed further in patients with epithelial ovarian cancer.

Importance of predosing of recombinant human thrombopoietin to reduce chemotherapy-induced early thrombocytopenia.

PURPOSE: Recombinant human thrombopoietin (rhTPO) increases platelets, and the peak response of rhTPO is delayed and is, therefore, not uniformly effective when administered after chemotherapy. The purpose of this study was to identify an effective schedule of rhTPO to best attenuate early thrombocytopenia. PATIENTS AND METHODS: Cohorts of six patients with sarcoma (66 assessable patients) were treated sequentially with doxorubicin and ifosfamide (AI), with rhTPO by a fixed dose and varying schedules being administered before and/or after chemotherapy in cycle 2 and subsequent cycles. Cycle 1 without rhTPO served as an internal control. RESULTS: AI causes cumulative thrombocytopenia. The platelet nadir in cycle 2 was higher than in cycle 1 (mean nadir +/- SEM, 119 +/- 12 x 10(3)/microL v 80 +/- 7 x 10(3)/microL, respectively; P <.001) in 24 (80%) of the 30 patients (P <.001) in whom rhTPO (1.2 microg/kg) was administered starting from 5 days before chemotherapy (pre/postdoses, three/one or one/one) compared with only four (17%) of 24 patients given rhTPO by other schedules (pre/postdoses, two/two, one/three, zero/four, or four/zero) and none of 15 historical control patients. The need for platelet transfusions in four cycles was significantly lower (13 [11%] of 114 cycles, P <.001) in patients who received rhTPO from day -5 (pre/post doses, three/one or one/one) compared with patients who received rhTPO at later time points (28 [47%] of 60 cycles). Bone marrow megakaryocytes increased markedly (four-fold) before chemotherapy with predosing rhTPO and remained elevated (two-fold) after chemotherapy, which may explain the possible mechanism for response. One patient developed subclavian vein thrombosis, and no patients developed neutralizing antibodies to rhTPO. CONCLUSION: These results demonstrate the importance of timing of rhTPO in relation to chemotherapy and indicate that, by optimizing the timing, only two doses of rhTPO (one before and one after chemotherapy) were required to significantly reduce the severity of chemotherapy-related early thrombocytopenia.

Safety and efficacy of transfusions of autologous cryopreserved platelets derived from recombinant human thrombopoietin to support chemotherapy-associated severe thrombocytopenia: a randomised cross-over study.

BACKGROUND: The increasing demand for platelet products, and concern over the transfusion-associated risks of alloimmunisation and infections, have motivated a search for improved methods aimed at keeping exposure to donor antigens to a minimum. Transfusion of thrombopoietin-derived autologous platelets might provide an alternative strategy. We aimed to compare the safety and efficacy of this strategy with that of transfusion with fresh allogeneic platelets in patients with severe chemotherapy-induced thrombocytopenia. METHODS: 20 patients with gynaecological malignancies were treated with two doses of 1.2 microg/kg recombinant human thrombopoietin. From day 12, we aimed to collect 50 units of platelets from these patients by plateletpheresis. Harvested platelets were cryopreserved in ThromboSol and 2% dimethyl sulfoxide (DMSO) for use in subsequent autologous transfusions. Patients then received carboplatin for up to six cycles. Patients were randomly assigned to group A (n=10), which received allogeneic fresh platelets at the first instance of severe thrombocytopenia (platelet count <15,000/microL) and then autologous cryopreserved platelets at the next, or to group B (n=10), which received first autologous and then allogeneic platelets. In subsequent cycles, all patients received autologous platelets while available. The primary endpoint was platelet count increment corrected for the number of platelets transfused and the patients' body-surface area. Analysis was by intention to treat. FINDINGS: Treatment with recombinant human thrombopoietin significantly increased platelet count (median 2.3-fold [range 1.5-3.3], p<0.0001) in all but one patient in group A. The median number of platelets collected per patient was 53 units (14-66) in two collections (one to three). There was no significant difference in the corrected platelet count increments (CCIs) between the 19 paired transfusions of cryopreserved autologous platelets and fresh allogeneic platelets (median 1-h CCI 15.7 vs 19.8, p=0.398; median 24-h CCI 13.0 vs 18.1, p=0.398). 14 of the 19 patients had a good response (1-h CCI >7.5) to their first transfusion of allogeneic platelets. By contrast, all patients had a good response to their first transfusion of autologous platelets (p=0.063). Moreover, no significant decrease in the CCIs (p=0.405) was seen over six cycles after autologous platelet transfusions (n=63). No transfusion reactions or any serious adverse event was recorded during autologous platelet transfusions. INTERPRETATION: Recombinant human thrombopoietin facilitated collection of multiple units of platelets, which could be cryopreserved and reinfused to counteract severe thrombocytopenia during multicycle chemotherapy. Transfusion of autologous cryopreserved platelets derived from recombinant human thrombopoietin can provide a viable strategy to minimise the risks of allogeneic platelet transfusions and provide a long-lasting supply of platelet support.