epoetin-alfa and Carcinoma--Small-Cell

The purpose of the current study was to investigate the role of amifostine and epoetin-alpha in reducing severe toxicities during concurrent chemo-hyperfractionated radiotherapy (CCRT) for limited disease small cell lung cancer (LD-SCLC).. Seventy-six patients with LD-SCLC were enrolled. The treatment schedule was consisted of two 28-day cycles of cisplatin at a dose of 30 mg/m2 (Days 1 and 8) and irinotecan at a dose of 60 mg/m2 (Days 1, 8, and 15) followed by two 21-day cycles of cisplatin at a dose of 60 mg/m2 (Day 1) and etoposide at a dose of 100 mg/m2 (Days 1-3) with concurrent twice-daily thoracic radiotherapy for a total of 45 grays. Patients were randomly assigned at registration to either amifostine at a dose of 500 mg or epoetin-alpha at a dose of 10,000 IU subcutaneously 3 times weekly (n = 36 patients and 40 patients, respectively). Fifteen of 36 patients assigned to the amifostine arm did not receive amifostine because of a lack of supply.. Amifostine treatment was associated with higher febrile neutropenia (P = .003) and grade 2 or 3 nausea (according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) (P = .03). It also demonstrated a trend toward higher grade 4 leukopenia (P = .05). Grade 3 esophagitis was reported in 30% of patients treated with amifostine and 9% of patients treated with epoetin-alpha (P = .059). Epoetin-alpha treatment was associated with less grade 2 or 3 anemia (P = .031) and lower decreases in hemoglobin level during CCRT (P = .016). The median survival times for both treatment arms were comparable (22.6 months in the amifostine arm vs 25.6 months in the epoetin-alpha arm; P = .447).. Although amifostine administered 3 times weekly during CCRT did not significantly reduce severe toxicities, epoetin-alpha was effective in preventing severe anemia during CCRT in patients with LD-SCLC. Other radioprotective strategies to minimize severe toxicities should be investigated.

Topics: Aged; Amifostine; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Combined Modality Therapy; Dose Fractionation, Radiation; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Humans; Injections, Subcutaneous; Lung Neoplasms; Male; Middle Aged; Radiation-Protective Agents; Recombinant Proteins; Survival Analysis

This randomized, double-blind, placebo-controlled trial (N93-004) evaluated the effects of epoetin alfa on tumor response to chemotherapy and survival in patients with small-cell lung cancer (SCLC).. Adult patients with hemoglobin < or = 14.5 g/dL starting chemotherapy received epoetin alfa 150 U/kg or placebo subcutaneously 3 times weekly until 3 weeks after completion of chemotherapy. Survival was assessed for 3 years. The primary end point was the proportion of patients with complete or partial response after three chemotherapy cycles.. The trial was terminated prematurely after 224 of a projected 400 patients were accrued. Baseline characteristics were similar between groups. Epoetin alfa and placebo patients (n = 109 and n = 115, respectively) had mean baseline hemoglobin of 12.8 g/dL and 13.0 g/dL, respectively. Overall tumor response was similar between the epoetin alfa and placebo groups after three chemotherapy cycles (72% and 67%, respectively; 95% CI of difference, -6% to 18%) and after completion of chemotherapy (60% and 56%, respectively; 95% CI of difference, -9% to 17%). Epoetin alfa and placebo groups had similar median overall survival (10.5 and 10.4 months, respectively) and overall mortality (91.7% and 87.8%, respectively; hazard ratio, 1.172; 95% CI, 0.887 to 1.549; P = .264). Hemoglobin was maintained in the prechemotherapy range in epoetin alfa patients, but decreased substantially in placebo patients. Fewer epoetin alfa patients than placebo patients required transfusion.. These results suggest that in newly diagnosed patients with SCLC epoetin alfa does not affect tumor response to chemotherapy or survival. However, the early trial closure makes these conclusions preliminary.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Lung Neoplasms; Middle Aged; Placebos; Recombinant Proteins; Survival Analysis

Non-small cell lung cancer (NSCLC) treatment with new drugs in combination with platinum salts induce anemia G1/2 and G3/4 WHO in about 35 and 10-20% of patients, respectively, with a chemotherapy (CT) dose intensity decrease in 20% of cases. Epoetin alfa, administered at standard dosages has been shown to significantly increase hemoglobin (Hb) levels, decrease transfusion requirements, and improve quality-of-life parameters in patients undergoing chemotherapy.. This open-label, non-randomized study was conducted to evaluate the efficacy and safety of an induction dose of epoetin alfa 40.000 IU in lung cancer patients with moderate or severe anemia who were receiving CT.. Twenty-four patients (8 SCLC and 16 NSCLC) were enrolled in the study to receive single subcutaneous (s.c.) injections of epoetin alfa 40.000 IU on days 1, 4, 7, 10, and 13, followed by standard treatment (10.000 IU t.i.w.) for the further 2 weeks. Nine patients had been previously treated with epoetin alfa 10.000 IU t.i.w. Twenty-two patients were receiving first-line CT and two patients were receiving docetaxel as second-line CT.. After 15 days of treatment, in 21 evaluable patients, Hb was 10.5 +/- 1.3 g/dL (mean +/- S.D.), with a mean increase from baseline of 2.0 g/dL (95%CI: 1.3-2.7). Hb increase was > or =2g/dL in 11 patients, 1-1.9 g/dL in 5 patients, and <1g/dL in 5 patients. After 30 days of treatment, Hb was 11.5 +/- 0.8 g/dL (mean +/- S.D.), with a mean increase from baseline of 2.9 g/dL (95%CI: 2.4-3.4) in 20 evaluable patients. No adverse events possibly related to epoetin alfa treatment were observed.. An induction therapy with epoetin alfa 40.000 IU for 2 weeks followed by standard treatment allows an Hb increase of 2.9 g/dL even in advanced lung cancer patients with a moderate/severe anemia, without RBC transfusion requirements. A randomized study of the proposed induction dose of epoetin alfa 40.000 IU is actually ongoing.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Lung Neoplasms; Male; Middle Aged; Recombinant Proteins; Treatment Outcome

Anaemia commonly occurs in cancer patients receiving chemotherapy, often necessitating blood transfusion. This multicentre study was designed to evaluate the efficacy and safety of epoetin alpha in preventing the decline in haemoglobin (Hb) level, and to determine whether the transfusion requirement could be reduced, in patients receiving 4-6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer (SCLC). A total of 130 non-anaemic SCLC patients were randomized to receive no additional treatment (n = 44), epoetin alpha 150 IU kg(-1) subcutaneously (s.c.) three times a week (n = 42) or 300 IU kg(-1) s.c. three times a week (n = 44). Reductions in epoetin alpha dosage were made during the study if Hb level increased to >15 g dl(-1). The mean weekly dosage was 335 and 612 IU kg(-1), respectively, in the two active treatment groups. Significantly fewer (P < 0.05) epoetin alpha-treated patients experienced anaemia (Hb < 10 g dl(-1)) during the course of chemotherapy (300 IU kg(-1), 39%; 150 IU kg(-1), 48%; untreated, 66%). This was reflected in the significantly lower number of treated patients transfused [300 IU kg(-1), 20% (P< 0.001); 150 IU kg(-1), 45% (P< 0.05); untreated, 59%]. Epoetin alpha was well-tolerated, and there was no evidence of sustained, clinically significant, hypertension. In summary, epoetin alpha is effective and well-tolerated in maintaining Hb level and reducing transfusion requirement in patients undergoing cyclic chemotherapy for SCLC.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Cisplatin; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Quality of Life; Recombinant Proteins