Use of darbepoetin alfa in European clinical practice for the management of chemotherapy-induced anaemia in four tumour types: final data from the CHOICE study.

OBJECTIVES: The CHOICE study was a prospective, multicentre, observational study designed to assess levels of adherence in current clinical practice to the European product label and EORTC guidelines for the treatment of chemotherapy-induced anaemia (CIA) with darbepoetin alfa (DA). Here we present data split by tumour types: breast, colorectal, ovarian and lung. METHODS: Haemoglobin (Hb) levels and red blood cell transfusion requirements were evaluated among patients with solid tumours in 11 European countries. The primary outcome measure was the proportion of patients with a target Hb level of ≥10-≤12 g/dL. RESULTS: The full analysis set included 1887 patients (mean ± SD 62.4 ± 11.4 years); 1585 (84%) had a current disease stage of ≥3. Common chemotherapy regimens were non-platinum + non-taxane based (n = 696 [37%]) or platinum + non-taxane based (n = 660 [35%]). Breast cancer (n = 575): The mean ± SD Hb level at baseline was 9.9 ± 0.8 g/dL (n = 568). Target Hb level was reached by 187 (55%) patients. Colorectal cancer (n = 310): At baseline the mean ± SD Hb level was 9.8 ± 0.8 g/dL (n = 306). Target Hb level was reached by 107 patients (56%). Ovarian cancer (n = 301): The mean ± SD Hb level at baseline was 9.7 ± 0.8 g/dL (n = 294). Target Hb level was reached by 81 patients (44%). Lung cancer (n = 701): At baseline the mean ± SD Hb level was 9.8 ± 0.9 g/dL (n = 692). Target Hb level was reached by 142 patients (39%). SAFETY: Five severe or life-threatening adverse drug reactions were seen (three patients with breast cancer, one patient with colorectal cancer and one patient with ovarian cancer). LIMITATIONS: Potential bias could not be excluded due to the study's observational nature. CONCLUSIONS: This study demonstrates that the recommendations are adhered to in clinical practice, with the mean starting Hb level <10 g/dL irrespective of tumour type. Furthermore, DA is likely to be effective and well tolerated for the treatment of CIA in patients with breast, colorectal, ovarian or lung cancer.

A final analysis from the CHOICE study examining darbepoetin alfa use for chemotherapy-induced anaemia in current European clinical practice.

OBJECTIVES: The CHOICE study was a prospective, multicentre, observational study designed to assess the level of adherence in current clinical practice to the European product label and the EORTC guidelines for the treatment of chemotherapy-induced anaemia with darbepoetin alfa (DA). METHODS: Hb levels and red blood cell (RBC) transfusion requirements were evaluated among 1900 patients with solid tumours in 11 European countries. The primary outcome measure was the proportion of patients with a target Hb level of ≥10-≤12 g/dL after 9 weeks' DA treatment. RESULTS: The full analysis set (FAS) comprised 1887 patients (mean ± SD age 62.4 ± 11.4 years) divided into categories by baseline Hb < 9 g/dL (n = 281); 9-<10 g/dL (n = 770); 10-<11 g/dL (n = 695); ≥11 g/dL (n = 114). The proportion of patients who remained on the study at week 9 achieving the target Hb level was 37% (n = 60), 48% (n = 217), 54% (n = 210) and 38% (n = 23) in the subgroups with a baseline Hb level of <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and ≥11 g/dL, respectively. In the <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and ≥11 g/dL subgroups of the FAS, the number of patients maintaining Hb levels ≥10 g/dL after their first achievement of an Hb value of 10 g/dL was 95 (34%), 372 (48%), 476 (68%) and 87 (76%), respectively. The Kaplan-Meier percentages of patients who required an RBC transfusion from week 5 until end of treatment period were: 29%, 20%, 12% and 17% in the <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and ≥11 g/dL subgroups, respectively. Kaplan-Meier percentages of patients reaching an Hb level of >13 g/dL were 10%, 9%, 21% and 29%, respectively. Potential bias could not be excluded due to the study's observational nature. CONCLUSIONS: DA initiation and target Hb ranges adhered to current guidelines in the majority of patients. Furthermore, this study demonstrates faster achievement of the target range and reduced transfusion requirements are associated with initiation of DA at Hb levels of 9-<10 g/dL and 10-<11 g/dL rather than <9 g/dL.

Current practice of darbepoetin alfa in the management of haemoglobin levels in cancer patients undergoing chemotherapy - data from the CHOICE study.

OBJECTIVE: To evaluate adherence to European Organisation for Research and Treatment of Cancer (EORTC) and European Summary of Product Characteristic (SmPC) guidance on recommended haemoglobin (Hb) values in routine clinical practice use of darbepoetin alfa (DA) in cancer patients internationally. METHODS: This multicentre, prospective, observational study assessed DA use in 11 European countries. This interim analysis (IA) included ∼1300 breast, colorectal, ovarian or lung cancer patients receiving DA during any chemotherapy cycle. Hb level and red blood cell (RBC) transfusion requirement data were collected. RESULTS: Of the 1290 patients (mean [SD] age 62.5 [11.1] years) included in this IA full analysis set, 499 had lung, 387 breast, 192 colorectal and 212 ovarian cancer. Mean baseline Hb levels were <10 g/dL. At week 9, 426 (33%) patients had a Hb level of 10-12 g/dL, 165 (13%) of >12 g/dL, 226 (18%) of <10 g/dL and 473 (37%) had missing Hb values. 54% of the 672 patients still on the study at week 9 with available Hb values had Hb values of 10-12 g/dL. For patients with a baseline Hb of <10 g/dL, the Kaplan-Meier (K-M) percentage of patients with Hb levels ≥10 g/dL from week 1 to end of treatment period (EOTP) was 86%. For these patients, the K-M% of patients with Hb levels >13 g/dL from week 1 to EOTP was 10%. The K-M% of patients requiring RBC transfusions from week 5 to EOTP was 26% for all patients. Seven patients reported treatment-related non-serious adverse drug reactions, four were thromboses. CONCLUSIONS: This IA suggests most patients were treated according to European SmPC guidance. Hb evolution during the study is consistent with data from clinical trials, implying DA is effective in increasing Hb levels in chemotherapy-induced anaemia patients. Hb levels >13 g/dL were infrequent. Limitations are related to the observational nature of this study.

A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy.

BACKGROUND: We evaluated the efficacy of a single fixed 6 mg dose of pegfilgrastim (a pegylated version of filgrastim) per cycle of chemotherapy, compared with daily administration of filgrastim, in the provision of neutrophil support. PATIENTS AND METHODS: Patients (n = 157) were randomized to receive either a single 6 mg subcutaneous (s.c.) injection of pegfilgrastim or daily 5 mg/kg s.c. injections of filgrastim, after doxorubicin and docetaxel chemotherapy (60 mg/m(2) and 75 mg/m(2), respectively). Duration of grade 4 neutropenia, depth of neutrophil nadir, incidence of febrile neutropenia, time to neutrophil recovery and safety information were recorded. RESULTS: A single 6 mg injection of pegfilgrastim was as effective as daily injections of filgrastim for all efficacy measures for all cycles. The mean duration of grade 4 neutropenia in cycle 1 was 1.8 and 1.6 days for the pegfilgrastim and filgrastim groups, respectively. Results for all efficacy end points in cycles 2-4 were consistent with the results from cycle 1. A trend towards a lower incidence of febrile neutropenia was noted across all cycles with pegfilgrastim compared with filgrastim (13% versus 20%, respectively). A single fixed dose of pegfilgrastim was as safe and well tolerated as standard daily filgrastim. CONCLUSIONS: A single fixed dose of pegfilgrastim administered once per cycle of chemotherapy was comparable to multiple daily injections of filgrastim in safely providing neutrophil support during myelosuppressive chemotherapy. Pegfilgrastim may have utility in other clinical settings of neutropenia.

Estrogen replacement therapy in women with a history of breast cancer.

Estrogens are known as potent mammary mitogen substances and are the major stimulus for the growth of hormone-dependent tumors and clearly implicated in the pathogenesis of breast cancer. Therefore it is a general belief that hormone replacement therapy (HRT) after breast cancer will increase the risk of developing recurrences, though there are no clear data available to support this suggestion. No prospective study with a large number of patients and a long treatment period was performed concerning this issue. On the other hand it may not be justifiable to withhold hormone replacement therapy from low-risk patients after menopause, knowing the benefits of this therapy concerning osteoporosis and cardiovascular advantages. Nevertheless, until appropriate clinical trials help to resolve this problem, non hormonal alternatives constitute the standard of care. One possible approach is to treat menopausal women who have had breast cancer symptomatically and avoid ERT unless absolutely necessary. The risk of cardiovascular diseases can be reduced with lifestyle. Tamoxifen has a beneficial effect on serum lipids and the intake for 5 years leads to a 50% reduction in the incidence of fatal myocardial infarction and a decrease in morbidity associated with ischaemic heart disease. Low doses of progestogen is effective for menopausal hot flushes. Tibolone reduces vasomotoric symptoms such as hot flushes and offers benefit on osteoporosis and has shown a significant reduction in high-density lipoprotein cholesterol. Whether replacing of estrogens is safe for patients after breast cancer remains uncertain. There is a need for a large controlled clinical trial to evaluate the safety and advantages of long time estrogen replacement in women treated for breast cancer.

[Oral contraceptives and breast cancer--a causal relationship?]. / Orale Kontrazeptiva und Bustkrebs--ein kausaler Zusammenhang.

Concern about the relationship between oral contraceptives, which have been used by more than 200 million women, and the risk of breast cancer has been present since three decades. Early studies showed no consistent results, but some authors are concerned about several subgroups having possibly an increased risk of developing breast cancer. A meta-analysis representing 90% of the data available on the topic showed a small but significant increase in the relative risk of developing breast cancer in women currently using oral contraception (1.24). This risk decreases after oral contraceptives have been ceased (1.16-1.07) and is comparable after 10 years to that of controls.