losartan-potassium and Ovarian-Neoplasms

Recombinant human erythropoietin (rhEPO) is used in breast and ovarian cancer patients to alleviate cancer- and chemotherapy-related anemia. Some clinical trials have reported that rhEPO may adversely impact survival and increase the risk of thrombovascular events in patients with breast cancer but not with ovarian cancer. The latter may potentially benefit the most from rhEPO treatment due to the nephrotoxic and myelosuppresive effects of standard platinum-based chemotherapy used in ovarian cancer disease. However, over the last decade the preclinical data have revealed that EPO is not only the principal growth factor and the hormone which regulates erythropoiesis, but also a cytokine with a pleiotropic activity which also can affect cancer cells. EPO can stimulate survival, ability to form metastases and drug resistance not only in continuous breast- and ovarian cancer cell lines but also in breast cancer stem-like cells. EPO receptor (EPOR) can also be constitutively active in both these cancers and, in breast cancer cells, may act in an interaction with estrogen receptor (ER) and epidermal growth factor receptor-2 (HER-2). EPOR, by an EPO-independent mechanism, promotes proliferation of breast cancer cells in cooperation with estrogen receptor, resulting in decreased effectiveness of tamoxifen treatment. In another interaction, as a result of the molecular antagonism between EPOR and HER2, rhEPO protects breast cancer cells against trastuzumab. Both clinical and preclinical evidence strongly suggest the urgent need to reevaluate the traditional use of rhEPO in the oncology setting.

Topics: Antineoplastic Agents; Breast Neoplasms; Drug Resistance; Erythropoietin; Female; Humans; Ovarian Neoplasms; Receptors, Erythropoietin; Recombinant Proteins; Signal Transduction; Vascular Diseases

The purpose was to conduct an integrated analysis of the cumulative hematologic toxicity of topotecan in patients with relapsed ovarian cancer and small cell lung cancer (SCLC). Data were pooled from eight phase II and phase III clinical studies performed in patients with relapsed stage III/IV ovarian cancer or extensive SCLC treated with topotecan at a dose of 1.5 mg/m(2) per day on days 1-5 of a 21-day course. Quantitative hematologic toxicities were assessed using the National Cancer Institute Common Toxicity Criteria. A total of 4,124 courses of therapy was administered to the 879 patients in the pooled population. Grade 4 neutropenia was experienced by 78% of patients. The lowest nadirs for neutrophils and platelets generally occurred after the first course of therapy, followed by improvement or stabilization in subsequent courses. Neutropenia was noncumulative. During the first course, significant risk factors were identified: renal impairment and advanced age (grade 3/4 thrombocytopenia and grade 4 neutropenia) and prior radiotherapy; performance status score > or =2; SCLC; and exposure to both cisplatin (Platinol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and carboplatin (Paraplatin; Bristol-Myers Squibb) (grade 3/4 thrombocytopenia only). The most frequent interventions for hematologic toxicities were RBC transfusions, treatment delays, G-CSF support, and dose reductions. Analysis of neutrophil and platelet nadirs and dosing for each course of therapy showed no apparent evidence of cumulative neutropenia or thrombocytopenia. The risk of grade 3 or 4 anemia was higher during the first four courses of therapy and may need to be more aggressively managed with erythropoietin therapy.

Topics: Antineoplastic Agents; Bone Marrow; Carcinoma, Small Cell; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Ovarian Neoplasms; Topotecan

Ovarian cancer is one of the most aggressive gynecologic cancers. It shows its symptoms late and is consequently often diagnosed at an advanced stage. The search for a more effective chemotherapy regimen, therefore, is of great importance. Since 1996, the combination of cisplatin and paclitaxel has been proven to prolong survival in comparison with older regimens containing cisplatin and cyclophosphamide. In addition, the introduction of carboplatin in combination with paclitaxel showed similar efficacy but preferable toxicity profiles when compared with cisplatin in combination with paclitaxel. Representative studies evaluating paclitaxel combination therapies as well as new trends in the treatment of ovarian cancer are summarized in this article.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Erythropoietin; Female; Hematinics; Humans; Ovarian Neoplasms; Paclitaxel; Recombinant Proteins

A Consensus Conference on the use of recombinant human erythropoietin (rHuEPO, epoetin alfa) in gynecologic tumors was held in Rome in March 1999, and an associated consensus paper has been published in Italian. The current paper updates several discussions that took place at the 1999 meeting concerning epoetin alfa treatment in breast, ovarian, and cervical cancers; the role of epoetin alfa in mobilizing progenitor hematopoietic cells; administration of epoetin alfa in combination with granulocyte colony-stimulating factor; and the effect of hemoglobin levels on outcome of radiation or chemoradiation treatment.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Female; Genital Neoplasms, Female; Granulocyte Colony-Stimulating Factor; Hematinics; Hematopoietic Stem Cell Mobilization; Hemoglobins; Humans; Ovarian Neoplasms; Quality of Life; Radiotherapy, Adjuvant; Recombinant Proteins; Uterine Cervical Neoplasms

Anemia is a common complication of myelosuppressive chemotherapy that results in a decreased functional capacity and quality of life (QOL) for cancer patients. Severe anemia is treated with red blood cell transfusions, but mild-to-moderate anemia in patients receiving chemotherapy has traditionally been managed conservatively on the basis of the perception that it was clinically unimportant. This practice has been reflected in the relative inattention to standardized and complete reporting of all degrees of chemotherapy-induced anemia. We undertook a comprehensive review of published chemotherapy trials of the most common single agents and combination chemotherapy regimens, including the new generation of chemotherapeutic agents, used in the treatment of the major nonmyeloid malignancies in adults to characterize and to document the incidence and severity of chemotherapy-induced anemia. Despite identified limitations in the grading and reporting of treatment-related anemia, the results confirm a relatively high incidence of mild-to-moderate anemia. Recent advances in assessing the relationships of anemia, fatigue, and QOL in cancer patients are providing new insights into these closely related factors. Clinical data are emerging that suggest that mild-to-moderate chemotherapy-induced anemia results in a perceptible reduction in a patient's energy level and QOL. Future research may lead to new classifications of chemotherapy-induced anemia that can guide therapeutic interventions on the basis of outcomes and hemoglobin levels. Perceptions by oncologists and patients that lesser degrees of anemia must be endured without treatment may be overcome as greater emphasis is placed on the QOL of the oncology patient and as research provides further insights into the relationships between hemoglobin levels, patient well-being, and symptoms.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials as Topic; Colorectal Neoplasms; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Head and Neck Neoplasms; Hematinics; Humans; Incidence; Lung Neoplasms; Lymphoma; Middle Aged; Neoplasms; Ovarian Neoplasms; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

A prospective phase II multicenter study was performed in two steps in paclitaxel-treated ovarian cancer patients in France. A French version of the four-item Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire was validated. This was then used to evaluate neurotoxicity in relation to erythropoietin treatment.. Patients received standard second-line paclitaxel-based chemotherapy and erythropoietin for anemia. Neurotoxicity and hemoglobin levels were evaluated every cycle with the FACT/GOG-Ntx and NCI-CTCAE. The translated questionnaire was tested in 20 patients to confirm the translation accuracy. The final questionnaire was validated in 98 patients with internal consistency (Cronbach's coefficient) and item correlation (Pearson's r coefficient) tests. Neurotoxicity severity was analyzed according to erythropoietin intake (first three cycles versus no or late intake) and correlated with anemia.. Patients received a median of six paclitaxel cycles (range 1-9). Neurotoxicity was validated in 484 questionnaires. Internal consistency was excellent with Cronbach's coefficients of ≥0.89 at inclusion, after 3 cycles and at study end. Inter-question correlation was high with Pearson's coefficients of 0.65-0.85. FACT/GOG-Ntx and NCI-CTCAE severity scoring was similar. Globally, the incidence of severe neurotoxicity (FACT/GOG-Ntx and NCI-CTCAE) was found significantly higher in patients with severe anemia. Of 98 evaluable patients, 31 received erythropoietin during the first three cycles. Mean hemoglobin level was significantly lower in this group from baseline to cycle 4; however, these anemic patients with early EPO intake did not develop an increase rate of severe neurotoxicity.. The French FACT/GOG-Ntx questionnaire is a reliable and valid tool for assessing chemotherapy-induced neuropathy. This study raises the possibility that erythropoietin might play a neuroprotective role when administered with paclitaxel.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Erythropoietin; Female; France; Humans; Middle Aged; Neuroprotective Agents; Neurotoxicity Syndromes; Ovarian Neoplasms; Paclitaxel; Prospective Studies; Surveys and Questionnaires; Translations

This is the first clinical trial for Japanese to evaluate the dose-response and determine the clinically effective dose of darbepoetin alpha by weekly subcutaneously administration in anemic patients with lung cancer or ovarian cancer receiving chemotherapy.. Eligible patients were required to have anemia (hemoglobin level of 15.0 g/dl (for men) or 14.0 g/dl (for women), and reinstated at 50% of the previous weekly dose when the hemoglobin level decreased to

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Ovarian Neoplasms; Platinum Compounds; Quality of Life

This study was aimed at investigating the effectiveness and safety of once-weekly epoetin beta for anaemic cancer patients receiving chemotherapy.. A total of 104 patients with a haemoglobin level of /=2.0 g/dL; the haemoglobin response rate. Quality of life (QOL) was assessed using the Functional Assessment of Cancer Therapy-Anaemia (FACT-An) questionnaire.. The haemoglobin response rate was 66.3% among the 98 patients (breast cancer: n = 25; malignant lymphoma: n = 21; ovarian cancer: n = 20; lung cancer: n = 15; other cancers: n = 17) assessable for a haemoglobin response. Thirty-nine patients (39.8%) required a dose escalation to 54 000 IU. At the end of the study, QOL assessable patients (n = 96) showed a mean improvement in the FACT-An total fatigue subscale score (FSS) of 0.3 points from baseline. Patients with a haemoglobin response had a mean change in the total FSS of +3.2, compared with -3.4 for patients without a haemoglobin response. No serious adverse event of epoetin beta was observed.. Epoetin beta administered at an initial dose of 36 000 IU once-weekly was well tolerated, with increased haemoglobin levels and improved QOL in anaemic cancer patients receiving myelosuppressive chemotherapy.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoietin; Female; Hemoglobins; Humans; Lung Neoplasms; Lymphoma; Male; Middle Aged; Ovarian Neoplasms; Patient Compliance; Quality of Life; Recombinant Proteins

This multicentre, open-label, controlled clinical trial assessed the effects of epoetin alfa treatment on haematologic and quality of life (QOL) parameters in 182 anaemic (Hb< or = 12 g dl(-1)) ovarian cancer patients receiving platinum chemotherapy. Patients were randomised 2 : 1 to receive epoetin alfa 10,000-20 000 IU three times weekly plus best standard treatment (BST) or BST only. Main study end points were changes from baseline in haemoglobin (Hb) level, transfusion requirements, and QOL. For the epoetin alfa group, mean Hb increased by 1.8 g dl(-1) by weeks 4-6 and was significantly increased from baseline through study end (P<0.001). The mean change in Hb from baseline was significantly (P<0.001) greater for epoetin alfa than BST patients at all post-baseline evaluations. Significantly fewer epoetin alfa than BST patients required transfusion(s) after the first 4 weeks of treatment (7.9 vs 30.5%; P<0.001). Also, significant (P< or = 0.04) differences favouring the epoetin alfa group over the BST group were found for all three median CLAS scores (Energy Level, Ability to Do Daily Activities, Overall QOL) and the median average CLAS score during chemotherapy. These findings support use of epoetin alfa to increase Hb levels, reduce transfusion use, and improve QOL in anaemic ovarian cancer patients receiving platinum chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Blood Transfusion; Cisplatin; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Middle Aged; Ovarian Neoplasms; Quality of Life; Recombinant Proteins

The effectiveness of every-three-week administration of darbepoetin alfa in women with chemotherapy-associated anemia was evaluated.. Women receiving chemotherapy for gynecological tumors who had a hemoglobin concentration of <10 g/dL were recruited from an obstetrics and gynecology service. Study patients received subcutaneous darbepoetin alfa 6.75 microg/kg, followed by 4.5 microg/kg every three weeks for a total of up to six doses. Hematopoietic response and mean changes in hemoglobin concentrations were evaluated. The Functional Assessment in Cancer Therapy-Anemia (FACT-An) survey was self-administered before and after study completion to evaluate the patients' quality of life.. The mean+/-S.D. age and weight for the 14 patients recruited (12 of whom were assessable) were 52.1+/-14 years and 64.6+/-19.8 kg, respectively. The mean initial and maintenance doses were 442 and 301.6 microg, respectively. The overall hematopoietic response was 64.3%, of which 35.7% were complete and 28.6% were partial. Peak response occurred at weeks 9 and 12. The mean+/-S.D. change in hemoglobin concentration was 1.6+/-1.51 g/dL. Treatment failure was predicted by week 9 (n=2). Maintenance doses were withheld if a patient's hemoglobin concentration exceeded 12 g/dL (n=3). The mean+/-S.D. point differential for FACT-An pretreatment and posttreatment scores was 5.8+/-4.71 (n=6).. Every-three-week administration of subcutaneous darbepoetin alfa produced a complete or partial hematopoietic response in 11 of 14 women with chemotherapy- associated anemia. A quality-of-life indicator generally improved among the 6 patients for whom posttreatment quality-of-life data were available.

Topics: Adult; Aged; Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Darbepoetin alfa; Drug Administration Schedule; Erythropoietin; Female; Hematopoiesis; Hemoglobins; Humans; Injections, Subcutaneous; Middle Aged; Ovarian Neoplasms; Pilot Projects; Prospective Studies; Quality of Life; Time Factors

This study evaluated the effects of low-dose IL-2 plus G-CSF/EPO on post-PBSC transplantation (PBSCT) immune-hematopoietic reconstitution and NK activity in patients with breast (BrCa) and ovarian cancer (OvCa). To this end, two consecutive series of patients were prospectively assigned to distinct post-PBSCT cytokine regimens (from day +1 to day +12) which consisted of G-CSF (5 microg/kg/day) plus EPO (150 IU/kg/every other day) in 17 patients (13 BrCa and 4 OvCa) or G-CSF/EPO plus IL-2 (2 x 10(5) IU/m(2)/day) in 15 patients (10 BrCa and 5 OvCa). Hematopoietic recovery and post-transplantation clinical courses were comparable in G-CSF/EPO- and in G-CSF/EPO plus IL-2-treated patients, without significant side-effects attributable to IL-2 administration. In the early and late post-transplant period a significantly higher PMN count was observed in G-CSF/EPO plus IL-2-treated patients (P = 0.034 and P = 0.040 on day +20 and +100, respectively). No significant differences were found between the two groups of patients in the kinetics of most lymphocyte subsets except naive CD45RA(+) T cells which had a delayed recovery in G-CSF/EPO plus IL-2 patients (P = 0.021 on day +100). No significant difference was observed between NK activity in the two different groups, albeit a significantly higher NK count was observed in G-CSF/EPO plus IL-2 series on day +20 (P = 0.020). These results demonstrate that low-dose IL-2 can be safely administered in combination with G-CSF/EPO early after PBSCT and that it exerts favorable effects on post-PBSCT myeloid reconstitution, but not on immune recovery.

Topics: Adult; Breast Neoplasms; Drug Therapy, Combination; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Growth Substances; Hematopoiesis; Hematopoietic System; Humans; Immune System; Interleukin-2; Killer Cells, Natural; Middle Aged; Ovarian Neoplasms; Peripheral Blood Stem Cell Transplantation; Prospective Studies; Transplantation, Autologous

The peripheral blood progenitor cell (PBPC) mobilization capacity of EPO in association with either G-CSF or sequential GM-CSF/G-CSF was compared in a randomized fashion after epirubicin, paclitaxel, and cisplatin (ETP) chemotherapy.. Forty patients with stage IIIB, IIIC, or IV ovarian carcinoma were enrolled in this randomized comparison of mobilizing capacity and myelopoietic effects of G-CSF + EPO and GM-/G-CSF + EPO following the first ETP chemotherapy treatment. After ETP chemotherapy (Day 1), 20 patients received G-CSF 5 microg per kg per day from Day 2 to Day 13 and 20 patients received GM-CSF 5 microg per kg per day from Day 2 to Day 6 followed by G-CSF 5 microg per kg per day from Day 7 to Day 13. EPO (150 IU per kg) was given every other day from Day 2 to Day 13 to all patients in both arms of the study. Apheresis (two blood volumes) was performed during hematologic recovery.. The magnitude of CD34+ cell mobilization and the abrogation of patients' myelosuppression were comparable in both study arms; however, GM-/G-CSF + EPO patients had significantly higher CD34+ yields because of a higher CD34+ cell collection efficiency (57.5% for GM-/G-CSF + EPO and 46.3% for G-CSF + EPO patients; p = 0.0009). Identical doses of PBPCs mobilized by GM-/G-CSF + EPO and G-CSF + EPO drove comparable hematopoietic recovery after reinfusion in patients treated with identical high-dose chemotherapy.. The sequential administration of GM-CSF and G-CSF in combination with EPO is feasible and improves the PBPC collection efficiency after platinum-based intensive polychemotherapy, associating high PBPC mobilization to high collection efficiency during apheresis.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Epirubicin; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Middle Aged; Ovarian Neoplasms; Paclitaxel

The ability of granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) treatment was compared in a randomized fashion with that of G-CSF treatment alone in promoting hematologic recovery and peripheral-blood progenitor-cell (PBPC) mobilization in previously untreated patients with advanced ovarian cancer who underwent their first course of epirubicin, paclitaxel, and cisplatin (ETP) chemotherapy during a phase II study of intensive outpatient ETP chemotherapy followed by high-dose carboplatin, etoposide, and melphalan (CEM) late intensification with PBPC support.. Comparative analysis of hematologic recovery of 50 randomized patients, after ETP chemotherapy, showed that life-threatening neutropenia occurred in 88% of the patients treated with G-CSF alone, whereas it occurred in only 4% of patients treated with G-CSF + EPO. Significantly different WBC and polymorphonuclear leukocyte (PMN) counts were observed in the two distinct arms on the day of WBC nadir (P <.0001 and P <.0001, respectively). Moreover, the addition of EPO to G-CSF increased PBPC mobilization and collection as compared with that in G-CSF-treated patients (P =.0009 and P =.0026, respectively), who required a significantly higher number of leukaphereses than G-CSF + EPO-treated patients (P =.0076) to obtain the planned minimum dose of PBPCs. Qualitative analysis by cloning assay of PBPCs collected in both arms revealed that G-CSF- and G-CSF + EPO-mobilized PBPCs have comparable in vitro functional properties.. This randomized comparison revealed that EPO significantly increases most of the hematologic effect produced by G-CSF administration after chemotherapy. This biologic property of EPO translated in vivo into a global improvement of patients' hematologic status.

Topics: Adult; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Cisplatin; Combined Modality Therapy; Drug Synergism; Epirubicin; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; Middle Aged; Neutropenia; Ovarian Neoplasms; Paclitaxel; Statistics, Nonparametric; Treatment Outcome

Patients with uterine or ovarian tumors frequently develop anaemia. Causes of anaemia in these patients are still not fully understood. We assessed serum erythropoietin (EPO) concentration in 70 women with benign or malignant uterine or ovarian tumors and in 43 control women. Thirteen women out of 50 with benign and 7 out of 20 with malignant tumors (26% and 35% respectively) were anaemic. In patients with benign tumors serum EPO concentrations did not differ from that in control subjects. In patients with malignant tumors plasma EPO was inappropriately low with respect to the haemoglobin concentration. From results obtained in this study it seems, that uterine or ovarian malignancy exerts a suppressive effect on EPO secretion. Inappropriately low EPO plasma concentration may account for the anaemia frequently occurring in these women.

Topics: Adult; Anemia; Erythropoietin; Female; Humans; Middle Aged; Ovarian Neoplasms; Uterine Neoplasms

This randomised controlled multicentre trial evaluated the effectiveness of recombinant human erythropoietin (rhEPO) in preventing anaemia and reducing the need for blood or erythrocyte transfusion in 122 ovarian cancer patients receiving platinum-based chemotherapy. The patients were randomly allocated to receive rhEPO 150 U/kg or 300 U/kg subcutaneously, three times a week, or open control. Patients also received up to 6 cycles of carboplatin or cisplatin, alone or in combination with other cytotoxic agents. Intention-to-treat analysis showed that 39.4% of patients in the control group received at least one blood transfusion, compared with 9.2% of patients treated with rhEPO. Patients treated with rhEPO experienced a significantly longer time to first erythrocyte transfusion than the control group and were less likely to experience nadir haemoglobin levels < 10 g/dl (P < 0.001 and < 0.05, respectively). A haemoglobin decrease < 1 g/dl during the first chemotherapy cycle, as well as a low baseline serum erythropoietin concentration, predicted a low transfusion need in rhEPO-treated patients but not in controls. During the study, 103 patients suffered at least one adverse event, but no serious, and only nine non-serious adverse events were considered possibly related to rhEPO therapy. These results indicate that treatment with rhEPO prevents anaemia, it reduces the need for blood or rhEPO erythrocyte transfusion in patients with ovarian cancer receiving platinum-based chemotherapy, and it is well tolerated. A starting dose of 150 U/kg of rhEPO, three times a week, may be recommended.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Erythropoietin; Female; Humans; Injections, Subcutaneous; Middle Aged; Ovarian Neoplasms; Platinum Compounds; Recombinant Proteins

The present report describes the non-haematological toxicity and the influence of growth factor administration on haematological toxicity and haematopoietic recovery observed after high-dose carboplatin (1200 mg m(-2)), etoposide (900 mg m(-2)) and melphalan (100 mg m(-2)) (CEM) followed by peripheral blood progenitor cell transplantation (PBPCT) in 40 patients with high-risk cancer during their first-line treatment. PBPCs were collected during the previous outpatient induction chemotherapy programme by leukaphereses. CEM administration with PBPCT was associated with low non-haematological toxicity and the only significant toxicity consisted of a reversible grade III/IV increase in liver enzymes in 32% of the patients. Haematopoietic recovery was very fast in all patients and the administration of granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) or granulocyte-macrophage colony-stimulating factor (GM-CSF) plus EPO after PBPCT significantly reduced haematological toxicity, abrogated antibiotic administration during neutropenia and significantly reduced hospital stay and patient's hospital charge compared with patients treated with PBPCT only. None of the patients died early of CEM plus PBPCT-related complications. Low non-haematological toxicity and accelerated haematopoietic recovery renders CEM with PBPC/growth factor support an acceptable therapeutic approach in an adjuvant or neoadjuvant setting.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carboplatin; Chemotherapy, Adjuvant; Erythropoietin; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Hematopoietic System; Humans; Length of Stay; Melphalan; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Recombinant Proteins; Survival Rate

In order to examine the influence of erythropoietin (rHuEPO) on serum hemoglobin levels, transfusion requirements, and quality of life in patients with gynecologic malignancies under polychemotherapy and chronic tumor anemia (hemoglobin <11 g/dl), we performed a prospective, randomized, double-blinded placebo-controlled clinical trial. Between October 1992 and October 1993, 35 patients from 5 gynecologic departments were entered into this trial. Inclusion criteria were hemoglobin level <11 g/dl, ferritin level >29 ng/ml, stool negative for occult blood, and life expectancy for more than 3 months. Patients received either 150 U/kg body wt rHuEPO (Erypo by Cilag-Janssen) sc three times a week for 12 weeks (n = 23) or a placebo (n = 12). If the hemoglobin levels of the 4th, 8th, or 12th week were >2 g/dl above the baseline value and/or >12 g/dl, the patient was classified as a responder. Patients who required blood transfusions (hemoglobin <8 g/dl, erythrocytes <3 x 10(6)/ml, or clinical symptoms of anemia) were classified as nonresponders. A nonvalidated quality of life questionnaire was completed by the patient at the beginning of the treatment and then every fourth week before receiving chemotherapy. In the rHuEPO group 56.6% of the patients responded to the treatment (chi2 = 10.79, P = 0.001) and only 5 patients (21.7%) required blood transfusions, whereas 8 of 12 patients in the placebo group (66.6%) had to be transfused (chi2 = 6.81, P = 0.009). Quality of life did not differ significantly between the rHuEPO group and the placebo group of patients. Within the rHuEPO group those patients that responded showed a significant increase in physical activity after response in comparison to the preresponsive phase (P = 0.02, paired t test). We therefore concluded that rHuEPO significantly increases serum hemoglobin levels and decreases transfusions requirements while maintaining quality of life in patients with gynecological malignancies who are undergoing polychemotherapy.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Double-Blind Method; Erythropoietin; Female; Humans; Middle Aged; Ovarian Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Uterine Neoplasms

In order to investigate the effects of erythropoietin (EPO) plus granulocyte colony-stimulating factor (G-CSF) administration after peripheral blood progenitor cell transplantation (PBPCT) we performed a phase I/II study in patients with high-risk cancer. 15 consecutive patients were treated wit recombinant human G-CSF (rhG-CSF) at the dose of 5 micrograms/kg subcutaneously (s.c.) every 24 h until day + 12 and with recombinant human EPO (rhEPO) at the dose of 150 IU/kg s.c. every 48 h until day + 11 following PBPCT. Their haemopoietic recovery was compared to that obtained in eight historic and control patients who did not receive any cytokines after PBPCT. No side-effects were observed during EPO plus G-CSF treatment and the treatment was not discontinued in any of the patients before completion of the treatment plan. The administration of EPO plus G-CSF after PBPCT produced a significant increase in the rate of white blood cell (WBC) (P = 0.0005), polymorphonuclear leucocyte (PMN) (P = 0.0005) and platelet (PLT) (P = 0.0105) recovery compared to the control group. The acceleration in haemopoietic recovery observed in the EPO plus G-CSF-treated patients produced a significant reduction of the days with WBC < 1 x 10(9)/l (P = 0.0009), PMN < 0.2 x 10(9)/l (P = 0.0030) and PMN < 0.5 x 10(9)/l (P = 0.0006). EPO plus G-CSF-treated patients required a significantly lower number of single donor PLT transfusions (P = 0.0142) and did not experience neutropenic fever, but historic control patients experienced fever > 38 degrees C for a median period of 4 d (0-12) with a medial period of parenteral antibiotic administration of 7.5 d (0-17). The length of the hospital stay was significantly shorter in the study group than in the historic control group (P = 0.0264). In conclusion, we can confirm that EPO plus G-CSF treatment is feasible and potentiates the haemopoietic recovery after PBPCT, thus simplifying the clinical management of cancer patients who undergo high-dose chemotherapy.

Topics: Adult; Breast Neoplasms; Combined Modality Therapy; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Middle Aged; Ovarian Neoplasms

Topics: Aged; Anemia; Antineoplastic Agents; Erythropoietin; Female; Humans; Middle Aged; Ovarian Neoplasms; Recombinant Proteins; Uterine Neoplasms

The introduction of carboplatin as a replacement for cisplatin into treatment strategies against ovarian cancer has ameliorated major toxicities related to cisplatin, but carboplatin-evoked myelosuppression requires further study, especially since the addition of growth factors for bone marrow and hematologic support has been introduced into clinical practice. Since higher doses of platinating agents seem to be related to higher response rates, the protective effect of interleukin-3 on 800 mg carboplatin, a twofold increment over the usual dose, was studied. A modest myeloprotective potency was documented in the second treatment cycle of this aggressive chemotherapy program, but this effect tapered away in subsequent treatment courses, which occasionally included severe side effects (eg, headache, kidney function impairments). Another study addressed the anemia frequently observed with both cisplatin- and carboplatin-based treatment regimens in ovarian cancer, which is probably related to low erythropoietin levels. Very preliminary analysis of an ongoing phase III trial studying two erythropoietin doses given continuously subcutaneously versus a retrospective analysis of a "control group" (drawn from historical data on the occurrence of anemia in cisplatin- and/or carboplatin-treated patients) has shown beneficial effects of erythropoietin during treatment with these platinating agents.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Erythropoietin; Female; Humans; Interleukin-3; Middle Aged; Neutropenia; Ovarian Neoplasms; Recombinant Proteins; Thrombocytopenia

Anemia is a frequent and potentially serious toxicity associated with the use of carboplatin, particularly when this agent is administered in the salvage setting. In an effort to evaluate a possible role for human erythropoietin (rh-E) in preventing or minimizing carboplatin-induced anemia we analyzed the impact of the agent on anemia and transfusion requirements of women with ovarian cancer who were treated on one of two nonrandomized trials employing identical second-line carboplatin-based intraperitoneal regimens, with the only difference in the regimens being the addition of rh-E (Study 1, without rh-E; Study 2, with rh-E). There was a statistically significant difference in the incidence of documented nadir hemoglobin levels of < 9 g/dl (Study 1, 60%; Study 2, 13%; P < 0.005) and < 8 g/dl (Study 1, 33%; Study 3, 6%; P < 0.05). We also observed a threefold reduction in transfusion requirements with the use of rh-E (Study 1, 23%; Study 2, 6%), but this difference was not statistically significant with the limited sample size evaluated. In this nonrandomized comparison of two identical chemotherapy programs we have demonstrated that rh-E significantly reduced the incidence and severity of anemia associated with carboplatin-based chemotherapy. A randomized trial examining the potential impact of rh-E on carboplatin-induced anemia and transfusion requirements is warranted.

Topics: Adult; Aged; Anemia; Carboplatin; Erythropoietin; Female; Humans; Middle Aged; Ovarian Neoplasms; Recombinant Proteins

Preliminary results from the first 21 patients of a group of 30 with International Federation of Gynaecology and Obstetrics (FIGO) stage II-IV epithelial ovarian carcinoma and anaemia are reported. Patients entered this open-label, comparative-group, out-patient study and were randomized to receive conventional support alone (control patients) or recombinant human erythropoietin (r-HuEPO) in addition to conventional support for 6 months. The aim of the study was to determine the effects of r-HuEPO on the anaemia induced by platinum-based chemotherapy. Patients randomized to r-HuEPO therapy received 300 U/kg subcutaneously 3 times weekly in addition to conventional chemotherapy. All patients underwent regular haematological monitoring. One patient developed a deep venous thrombosis after 17 doses of r-HuEPO; it was thought that this event may have been related to therapy and the patient was withdrawn from the study. Three other withdrawals occurred after 11, 15 and 40 doses of r-HuEPO because of progressive anaemia, metoclopramide-induced skin rash and change of chemotherapy, respectively. In the 21 patients analysed to date, there was a notable reduction in blood transfusion requirements during the 6 months of chemotherapy and an improvement in mean serial haemoglobin concentrations in patients on r-HuEPO compared with the control group. In conclusion, r-HuEPO has the potential for reducing haematological toxicity in patients with ovarian carcinoma receiving platinum-based chemotherapy. Also, r-HuEPO may allow modest dosage increments in chemotherapy or the addition of abdominopelvic radiotherapy.

Topics: Adult; Anemia; Carboplatin; Carcinoma; Cisplatin; Erythropoietin; Female; Humans; Middle Aged; Ovarian Neoplasms; Random Allocation; Recombinant Proteins

The aim of this study was to evaluate the efficacy and feasibility of a peri-operative bloodless medicine and surgery (BMS) protocol in reducing severe post-operative anaemia (haemoglobin [Hb] <7 g/dL) in Jehovah's Witnesses undergoing cytoreductive surgery for advanced epithelial ovarian cancer.. This was a single-institution retrospective study enrolling Jehovah's Witnesses who underwent elective bloodless surgery for advanced epithelial ovarian cancer between October 2017 and April 2020. All patients followed a standardised bloodless medicine and surgery protocol based on ferric carboxymaltose and erythropoietin if indicated.. The use of a multidisciplinary bloodless medicine and surgery protocol is safe and effective in reducing the rate of severe post-operative anaemia and improving surgical and oncological outcomes of Jehovah's Witnesses with advanced epithelial ovarian cancer. Further large-scale, prospective studies are required to confirm these data.

Topics: Anemia; Carcinoma, Ovarian Epithelial; Cytoreduction Surgical Procedures; Erythropoietin; Female; Hemoglobins; Humans; Jehovah's Witnesses; Middle Aged; Ovarian Neoplasms; Retrospective Studies

To determine the effectiveness of erythropoietin-stimulating agent (ESA) and granulocyte colony-stimulating factor (CSF) in reducing blood transfusion needs and neutropenia incidence in community-dwelling elderly ovarian cancer patients.. The SEER (Surveillance Epidemiology and End Results)-Medicare database was used to identify 5572 women with stage III/IV ovarian cancer who received chemotherapy. To assess clinical effectiveness, we categorized patients based on the number of administrations of ESA (ie, epoetin-alfa and darbepoetin-alfa) and CSF (ie, filgrastim and pegfilgrastim). To evaluate effect on survival, patients were categorized as receiving ESA only, CSF only, ESA + CSF, and no ESA/CSF.. Two thirds of patients received growth factor support (24% ESA only, 13% CSF only, 30% ESA + CSF). Depending on the number of epoetin-alfa administrations, ESA was associated with 48% to 56% lower need for blood transfusion compared with no ESA (hazard ratio for 1-3 claims, 0.47; 4-6 claims, 0.52; 7-10 claims, 0.48; ≥11 claims, 0.44). Patients who received at least 3 prophylactic filgrastim administrations had 71% to 98% lower risk of developing neutropenia (hazard ratio for 3-4 claims, 0.29; ≥5 claims, 0.02) compared with those without CSF. Effectiveness was comparable for darbepoetin-alfa and pegfilgrastim use. Overall survival was longer in those who received CSF only; however, the risk of mortality after 24 months was higher in those who received ESA (P = 0.0005). All models were adjusted for relevant covariates.. Erythropoietin-stimulating agents were effective in reducing blood transfusion need. Granulocyte colony-stimulating factors were effective in lowering neutropenia incidence and also were associated with improved survival in elderly ovarian cancer patients. Findings are consistent with clinical trials and clinical guidelines.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Combined Modality Therapy; Erythropoietin; Female; Filgrastim; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Incidence; Middle Aged; Needs Assessment; Neoplasm Staging; Neutropenia; Ovarian Neoplasms; Polyethylene Glycols; Prognosis; Recombinant Proteins; Retrospective Studies; SEER Program; Survival Rate

While recombinant human erythropoietin (rhEpo) has been widely used to treat anemia in cancer patients, concerns about its adverse effects on patient survival have emerged. A lack of correlation between expression of the canonical EpoR and rhEpo's effects on cancer cells prompted us to consider the existence of an alternative Epo receptor. Here, we identified EphB4 as an Epo receptor that triggers downstream signaling via STAT3 and promotes rhEpo-induced tumor growth and progression. In human ovarian and breast cancer samples, expression of EphB4 rather than the canonical EpoR correlated with decreased disease-specific survival in rhEpo-treated patients. These results identify EphB4 as a critical mediator of erythropoietin-induced tumor progression and further provide clinically significant dimension to the biology of erythropoietin.

Topics: Adult; Aged; Aged, 80 and over; Animals; Blotting, Western; Breast Neoplasms; Cell Line, Tumor; Disease Progression; Erythropoietin; Female; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; MCF-7 Cells; Mice, Inbred C57BL; Mice, Nude; Middle Aged; Ovarian Neoplasms; Protein Binding; Receptor, EphB4; Receptors, Erythropoietin; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; STAT3 Transcription Factor; Young Adult

Erythropoietin (Epo) is a key regulator of erythroid cell proliferation, differentiation and apoptosis. In the form of the recombinant protein, it is widely used to treat various types of anemias, including that associated with cancer and with the myelosuppressive effects of chemotherapy, particularly platinum-based regimens. Our previous studies confirmed the presence of Epo receptors (EpoRs) in ovarian adenocarcinoma cell lines and demonstrated that long-term Epo treatment of A2780 cells resulted in the development of a phenotype exhibiting both enhanced Epo signaling and increased paclitaxel resistance. In the present study, we carried out a series of experiments to analyze the pro-angiogenic potential of Epo-treated A2780 and SKOV-3 cells. Our studies revealed that conditioned media of Epo-treated A2780 cells had a stimulative effect on human umbilical vein endothelial cells (HUVECs). This effect was only seen when A2780 cells were incubated under hypoxic conditions. Furthermore, Epo increased the secretion of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, GM-CSF and interferon-γ by A2780 cells that grew in hypoxic conditions. In this regard, conditioned media of hypoxic and Epo-treated A2780 cells induced a significant phosphorylation of STAT-5 in HUVECs. Our results may have important implications for ovarian cancer patients receiving Epo.

Topics: Adenocarcinoma; Blotting, Western; Cell Proliferation; Culture Media, Conditioned; Enzyme-Linked Immunosorbent Assay; Epoetin Alfa; Erythropoietin; Female; Human Umbilical Vein Endothelial Cells; Humans; Hypoxia; Neovascularization, Pathologic; Ovarian Neoplasms; Real-Time Polymerase Chain Reaction; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured

Erythropoietin (Epo) is a critical regulator of erythroid cell proliferation, differentiation and apoptosis. In the form of a recombinant protein, it is widely used to treat various forms of anemia, including that associated with cancer and with the myelosuppressive effects of chemotherapy. Studies of ovarian cancer cell lines have demonstrated the presence of the Epo receptor (EpoR), but there are disagreements regarding its localization and functionality in these cells. Using fluorescence microscopy, we were not able to identify the EpoR on the surface of A2780 cells, in contrast to the positive control K562 cells. Flow cytometry did reveal a weak surface EpoR signal in A2780 cells. Interestingly, most of the EpoR in A2780 cells was found in the cytoplasm, more abundantly as an intracellular membrane-associated protein than a soluble one. Silencing EpoR expression by lentiviral-mediated shRNA resulted in reduced A2780 proliferation as well as reduction in Epo-induced phosphorylation of Erk1/2. Our findings provide important insights into the biology of the EpoR in ovarian cancer cells.

Topics: Cell Line, Tumor; Cell Membrane; Cell Proliferation; Endoplasmic Reticulum; Erythropoietin; Female; Gene Knockdown Techniques; Humans; Intracellular Membranes; Microscopy, Fluorescence; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Ovarian Neoplasms; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptors, Erythropoietin; RNA Interference; Secretory Vesicles

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.. 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.. 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%).. 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).. Potential bias could not be excluded due to the study's observational nature.. 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.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Breast Neoplasms; Colorectal Neoplasms; Darbepoetin alfa; Erythropoietin; Europe; Female; Hematinics; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Prospective Studies

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).. 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.. 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.. 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.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Breast Neoplasms; Colorectal Neoplasms; Darbepoetin alfa; Erythropoietin; Europe; Female; Guideline Adherence; Hematinics; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Practice Guidelines as Topic; Prospective Studies

Erythropoietin (Epo) is a glycoprotein that stimulates proliferation and migration of human endothelial cells and promotes angiogenesis, which are crucial phenomena in cancer biology. The objective of this study was to investigate whether Epo is detectable in the ascitic fluid of patients with ovarian tumors.. We investigated the presence of Epo in the ascitic fluid of 100 women undergoing laparotomy for an ovarian tumor. Epo concentration was quantitated with an immunochemiluminometric assay.. Ten women had a benign tumor, 13 women had a borderline tumor, and 77 women had ovarian cancer. Epo was detected in all ascitic fluid samples, in similar amounts as in corresponding serum samples. Ascitic fluid Epo concentration did not differ between the 3 study groups (P = 0.081), but in multiple comparisons, ascitic fluid Epo was higher in the women with cancer than in the women with a benign tumor (P = 0.006). Ascitic fluid Epo concentration correlated positively with serum Epo (P < 0.0001) and the volume of ascites (P < 0.0001). In regression analyses, serum Epo, volume of ascites, blood hemoglobin, plasma CA125, tumor stage, tumor grade, and the presence of residual tumor after surgery had no significant independent effect on ascitic fluid Epo.. Considerable amounts of Epo are present in the ascitic fluid of women with ovarian tumors. The origin of Epo in the ascitic fluid of women with ovarian tumors as well as the clinical relevance of our finding remain to be clarified.

Topics: Ascitic Fluid; Biomarkers, Tumor; CA-125 Antigen; Carcinoma, Ovarian Epithelial; Cystadenoma, Serous; Erythropoietin; Female; Hemoglobins; Humans; Membrane Proteins; Neoplasms, Glandular and Epithelial; Osmolar Concentration; Ovarian Cysts; Ovarian Neoplasms

The primary aim of palliative treatment is to improve the quality of life, followed by prolongation of overall survival. The effective regimens are usually complicated by increased side effects, particularly hematologic. Under these conditions, useful treatment is difficult and less effective.. We present the case of a patient with cancer of the abdominal and pelvic cavity (the origin was likely an ovary). The patient was treated with intensive chemotherapy (15 cycles of carboplatin and paclitaxel) and supportive care (30 doses of epoetin alpha and 2 doses of 48MIU G-CSF for neutropenia G4).. A good quality of life and long-term persistent complete remission (6 months) was achieved, no transfusion, no hospitalization. Overall survival was 61 months.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Epoetin Alfa; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hematinics; Humans; Ovarian Neoplasms; Recombinant Proteins

Ovarian carcinoma is the leading cause of death from gynecological cancers in many Western countries. Aberrant glycosylation is an important aspect in malignant transformation and consequently in ovarian cancer. In this study, a detailed structure analysis of the N-linked glycans from total glycoproteins from the SKOV3 ovarian carcinoma cell line and from a recombinantly expressed secretory glycoprotein, erythropoietin (EPO), produced from the same cells has been performed using high-performance anion exchange chromatography with pulsed amperometric detection and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Total cellular N-glycans contained high-mannose type and proximally fucosylated complex type partially agalactosylated structures. On the other hand, the recombinant human EPO secreted from SKOV3 cells contained predominantly core-fucosylated tetraantennary structures, which were partially lacking one or two galactose residues, and partially contained the LacdiNAc motif. Only minor amounts of di- and triantennary complex-type glycans were found, and high-mannose-type glycans were not present in the secreted EPO protein. A large amount of N-acetylneuraminic acid in α2,3-linkage was detected as well. Endogenous glycoproteins were also found to contain the LacdiNAc motif in N-linked glycans. This work contributes to the knowledge of the glycosylation of a human ovarian cancer cell line. It also establishes the basis to further explore high-mannose-type glycans, and the LacdiNAc motif as possible markers of ovarian carcinoma.

Topics: Biomarkers, Tumor; Erythropoietin; Female; Glycoproteins; Glycosylation; Humans; Lactose; Mannose; Molecular Structure; Ovarian Neoplasms; Polysaccharides; Recombinant Proteins; Tumor Cells, Cultured

Studies have suggested that erythropoietin-stimulating agents (ESAs) may affect progression-free survival (PFS) and overall survival (OS) in a variety of cancer types. Because this finding had not been explored previously in ovarian or primary peritoneal carcinoma, the authors of this report analyzed their ovarian cancer population to determine whether ESA treatment for chemotherapy-induced anemia affected PFS or OS.. A retrospective review was conducted of women who were treated for ovarian cancer at the corresponding author's institution over a 10-year period (from January 1994 to May 2004). Treatment groups were formed based on the use of an ESA. Two analyses of survival were conducted to determine the effect of ESA therapy on PFS and OS. Disease status was modeled as a function of treatment group using a logistic regression model. Kaplan-Meier curves were generated to compare the groups, and a Cox proportional hazards model was fit to the data.. In total, 343 women were identified. The median age was 57 (interquartile range, 48-68 years). The majority of women were Caucasian (n = 255; 74%) and were diagnosed with stage III (n = 210; 61%), epithelial (n = 268; 78%) ovarian cancer. Although the disease stage at diagnosis and surgical staging significantly affected the rates of disease recurrence and OS, the receipt of an ESA had no effect on PFS (P = .9) or OS (P = .25).. The current results indicated that there was no difference in cancer-related PFS or OS with use of ESA in this cohort of women treated for ovarian cancer.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Disease-Free Survival; Erythropoietin; Female; Humans; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Recombinant Proteins; Retrospective Studies; Survival Analysis

Topics: Antibody Specificity; Cell Line, Tumor; Erythropoietin; Extracellular Signal-Regulated MAP Kinases; Female; Humans; Ovarian Neoplasms; Phosphorylation; Receptors, Erythropoietin; Recombinant Proteins

Although recombinant human erythropoietin (rHuEpo) has revolutionized the treatment of anemia, recent clinical trials suggested that rHuEpo use may be associated with decreased survival in cancer patients. Although the expression of erythropoietin (Epo) receptor (EpoR) has been demonstrated in various human cancers, the effect of exogenous Epo on the growth and therapy resistance of EpoR-bearing tumor cells is unclear at present. In the current study, we examined the hypothesis that EpoR may contribute to tumor growth independent of Epo in A2780 human ovarian carcinoma cells. A2780 human ovarian carcinoma cells showed high levels of EpoR expression, but lacked expression of Epo mRNA and biologically active Epo protein under both normoxic and hypoxic conditions. Exogenous Epo did not stimulate EpoR-mediated signaling, proliferation, invasiveness, or resistance to cytotoxic drugs in A2780 cells. In contrast, specific inhibition of EpoR expression using a short hairpin RNA (shRNA) expression plasmid resulted in markedly reduced proliferation and invasiveness in vitro. In addition, inhibition of EpoR expression led to abrogated in vivo ovarian cancer cell growth in a tumor xenograft system and resulted in decreased EpoR signaling. Our findings suggest that EpoR may be constitutively active in some cancer cells in the absence of Epo and provide the first evidence for a potential role of an Epo-independent, EpoR-mediated pathway in the growth of some human cancers.

Topics: Animals; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Disease Progression; Erythropoietin; Female; Flow Cytometry; Gene Expression; Humans; Immunohistochemistry; Male; Mice; Mice, Nude; Neoplasm Invasiveness; Ovarian Neoplasms; Receptors, Erythropoietin; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA, Messenger; Transfection; Xenograft Model Antitumor Assays

Recombinant human erythropoietin is widely used to treat anemia associated with cancer and with the myelosuppressive effects of chemotherapy, particularly platinum-based regimens. Erythropoietin is the principal regulator of erythroid cell proliferation, differentiation, and apoptosis. Recently, the antiapoptotic and proliferative effects of erythropoietin on nonhematopoietic cells were also established. We now show the effect of erythropoietin treatment on the response of A2780 and SKOV3 ovarian carcinoma cell lines to photodynamic therapy (PDT) using hypericin. SKOV3 exhibited an increased resistance to hypericin when cells were treated with erythropoietin. This resistance was reversed by treatment of SKOV3 cells with the specific Janus kinase 2 kinase inhibitor AG490 or the tyrosine kinase inhibitor genistein. These results support a role for the specific erythropoietin-induced Janus kinase 2/STAT signal transduction pathway in PDT resistance. Evidence of erythropoietin signaling was obtained by the demonstration of Akt phosphorylation in both A2780 and SKOV3 cells. Erythropoietin-treated SKOV3 cells exhibited decreased apoptosis induced by hypericin, an effect that was blocked by the phosphoinositide 3-kinase/Akt inhibitor wortmannin. These results may have important implications for ovarian cancer patients undergoing PDT and receiving erythropoietin.

Topics: Apoptosis; Base Sequence; Cell Line, Tumor; DNA Primers; Erythropoietin; Female; Humans; Ovarian Neoplasms; Photochemotherapy; Recombinant Proteins

Erythropoietin (Epo), a glycoprotein hormone that is the principal regulator of erythropoiesis, is known to act also on nonhematopoietic cell types. Epo receptors have been reported on several normal and neoplastic human cells and tissues, including ovarian cancer cells. We found that long-term Epo treatment of A2780 cells resulted in the development of a phenotype exhibiting both enhanced Epo signaling, evidenced by increased peak levels of phospho-Erk1/2 and increased paclitaxel resistance. This phenotypic effect was specific for paclitaxel, since no change in cisplatin or carboplatin sensitivity was observed. In addition, the change in phenotype was stable, even after the removal of Epo. Measurement of mono- and oligonucleosome formation revealed that long-term Epo treated A2780 cells exhibited markedly less apoptosis than nonerythropoietin treated cells at essentially all concentrations of paclitaxel tested. Western blot analyses revealed that the long-term Epo treated cells had significantly reduced expression of apoptosis-related proteins Bcl-2 and Bcl-10. These findings may have implications for the clinical use of recombinant human Epo and other erythropoiesis stimulating agents to correct anemia in paclitaxel-treated cancer patients.

Topics: Adaptor Proteins, Signal Transducing; Antineoplastic Agents; Apoptosis; B-Cell CLL-Lymphoma 10 Protein; Carboplatin; Cell Line, Tumor; Cisplatin; Drug Resistance, Neoplasm; Erythropoietin; Female; Gene Expression Regulation, Neoplastic; Humans; Ovarian Neoplasms; Paclitaxel; Proto-Oncogene Proteins c-bcl-2; Recombinant Proteins; Signal Transduction

The identification of erythropoietin receptors (EpoR) on cancer cells has caused concern, since it implies the possibility that treatment of cancer patients with erythropoietin (Epo) and related agents with demonstrable antiapoptotic activity could enhance cancer growth and progression. However, the function and even the validity of the identification of these receptors have been called into question. We now report the characterization of EpoR and Epo expression by 4 human ovarian cancer cell lines: A2780, CaOV, SKOV and OVCAR-3. Using semiquantitative RT-PCR, restriction digestion of the PCR products and DNA sequence analysis, we determined that each of the lines expresses the EpoR and Epo at the mRNA level. A2780 cells were the highest expressers of both genes. We demonstrated EpoR protein both by western blotting and by immunofluorescence and biologically active Epo protein by quantitative in vitro bioassay. The EpoR on A2780 cells was shown to be functional, since Epo stimulation resulted in phosphorylation of Erk1/2, an important EpoR mitogenic signaling intermediate. None of the cell lines exhibited a growth response in culture to exogenous Epo. However, addition of a neutralizing anti-Epo antibody to A2780 cells resulted in partial growth inhibition that was reversed by the addition of excess Epo, providing evidence for an autocrine/paracrine mechanism of growth enhancement in these cells.

Topics: Apoptosis; Base Sequence; Cell Line, Tumor; DNA Restriction Enzymes; Erythropoietin; Female; Gene Expression Regulation, Neoplastic; Humans; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Molecular Sequence Data; Ovarian Neoplasms; Receptors, Erythropoietin; Sequence Homology, Nucleic Acid; Signal Transduction

Recombinant epoetin alfa and darbepoetin alfa (r-HuEPO) have been shown to be safe and effective treatments for anemia, but recent reports have suggested an increased risk of thromboembolic events when these agents are used to treat chemotherapy-induced anemia among patients with breast or ovarian cancer. We examined the possible risk of such events among patients with ovarian or primary peritoneal carcinomas and chemotherapy-induced anemia.. We retrospectively analyzed data over 10 years from women at one hospital with ovarian or primary peritoneal carcinoma and chemotherapy-induced anemia. The incidence and odds ratio for development of deep venous thrombosis, unadjusted and adjusted for baseline differences and risk factors, was assessed between patients who had received r-HuEPO versus no treatment for anemia.. Of the 364 women, 90 had received r-HuEPO and 253 had not. The incidence of deep venous thrombosis was 6.7% in the group that had received r-HuEPO and 5.1% in the group that had not (unadjusted odds ratio, 1.31; 95% confidence interval [CI], 0.48-3.55). After adjustment for differences in age, body-mass index, prior thromboembolic disease or cancer, and tobacco use, the odds ratio for developing deep venous thrombosis with the use of r-HuEPO was 1.35 (95% CI, 0.49-3.75).. The use of r-HuEPO was not associated with an increased risk of deep venous thrombosis in this population. A randomized trial is needed to further explore this issue and to detail the safety and efficacy of these agents in patients with various other cancers.

Topics: Aged; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Recombinant Proteins; Venous Thrombosis

Evaluation of the clinical efficacy and tolerance of metronomic chemotherapy as salvage therapy in a young patient with advanced, platinum resistant, ovarian carcinoma and bad performance status.. We tried palliative chemotherapy with daily low dose oral cyclophosphamide with a patient suffering from stage IIIC ovarian cancer that responded to daily cyclophosphamide (CTX) after no response to chemotherapy with paclitaxel and carboplatin as first line and progression after second line with topotecan. The progression-free survival time on daily low dose oral cyclophosphamide treatment was 65 months without side effects. She was well during the chemotherapy and lived a normal working and social life.. We think that use of low dose of oral CTX should be investigated further as a strategy against tumour progression after standard chemotherapy in patients who are platinum resistant with poor performance status.

Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Colonic Neoplasms; Colostomy; Cyclophosphamide; Cystadenocarcinoma, Serous; Disease-Free Survival; Drug Administration Schedule; Drug Evaluation; Drug Resistance, Neoplasm; Epoetin Alfa; Erythropoietin; Fatal Outcome; Female; Follow-Up Studies; Hemorrhage; Humans; Intestinal Obstruction; Karnofsky Performance Status; Laparotomy; Ovarian Neoplasms; Ovariectomy; Paclitaxel; Palliative Care; Peritoneal Neoplasms; Recombinant Proteins; Salvage Therapy; Topotecan; Urinary Bladder Neoplasms; Vitamins

To assess recent developments in the use of transfusions.. Data from hospital-based sources were condensed in a single spread sheet covering 1611 transfusions of a total of 881 patients together with data on 25,264 treatment sessions in 6137 patients within a time period between 1 August 2001 and 31 July 2004.. Our audit showed an increase in transfusions of 25% in 3 years. This was accompanied by an increased threshold for transfusions, as shown by a significant rise in mean haemoglobin trigger levels from 8.53 to 8.86 g/dl (P<0.001) as well as an increase in treatment sessions and patient numbers - especially for chemotherapy or combinations of chemotherapy and radiotherapy. The highest transfusion rates and also the greatest increments occurred in patients with carcinoma of the ovary, lung and pancreas. Within these groups, treatment regimens as well as treatment lines were additional predictive factors.. This audit gives a detailed view on rising trends in transfusion requirements and, in light of anticipated restrictions on resources, it identifies high-risk areas, where the use of alternatives, such as erythropoietin, could be considered.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Breast Neoplasms; Cost-Benefit Analysis; Database Management Systems; England; Erythropoietin; Female; Health Services Needs and Demand; Hemoglobins; Hospitals, University; Humans; Lung Neoplasms; Male; Medical Audit; Medical Oncology; Ovarian Neoplasms; Pancreatic Neoplasms; Radiation Oncology; Utilization Review

Paclitaxel (Taxol) is a drug derived from the bark of the Pacific yew tree and is widely used in cancer treatment, especially for breast, ovarian, and lung cancers. It has not previously been reported to induce lupus.. We report the case of a woman with ovarian cancer who developed paclitaxel-induced lupus on two occasions. Both times, the paclitaxel dramatically improved the ovarian cancer.. The diagnosis of lupus was confirmed by the initial skin appearance, elevated levels of antinuclear antibodies, recurrence on reintroduction, and biopsy results. To our knowledge, it is the first case reported of paclitaxel-induced lupus.

Topics: Aged; Anti-Inflammatory Agents; Antibodies, Antinuclear; Antineoplastic Agents, Phytogenic; Betamethasone; Biopsy; Drug Therapy, Combination; Erythropoietin; Female; Humans; Lupus Erythematosus, Cutaneous; Ovarian Neoplasms; Paclitaxel; Recombinant Proteins; Recurrence; Skin; Treatment Outcome

Thrombotic events are infrequently observed in erythropoietin treatments for the anemia in tumorous patients with chemotherapy. The manufacturers call attention to this possible side effect of all kind of such drugs.. To estimate the amount of thrombotic events in erythropoietin administrations during epoetin treatments for ovarian cancer patients treated with antineoplastic drugs.. 275 ovarian cancer patients were treated with erythropoietin in the Gynecologic Department at the National Institute of Oncology, Budapest, in the period between 2000 and 2006: 52 of them were given epoetin-alfa, 157 of them epoetin-beta and 66 of the patients received darbepoetin-alfa. Median age of the patients was 60 (ranges 22 and 84) years.. Thrombotic events were detected in 3 patients out of the 275: one with epoetin-alfa and two times with epoetin-beta treatment (3/275 = 1,1%). No definite causal relationship was confirmed between the thrombotic events and the erythropoietin drugs.. Thrombosis was infrequently monitored among the authors' patients similarly to the literature data.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Humans; Hungary; Incidence; Middle Aged; Ovarian Neoplasms; Recombinant Proteins; Retrospective Studies; Thrombosis

The objective of this study was to evaluate the effects of recombinant erythropoietin (EPO) on HIF-1alpha induced angiogenic pathways in ovarian cancer cells.. Using Western blots and both quantitative and non-quantitative RT-PCR, HIF-1alpha protein and VEGF transcription levels were assessed. Cell growth was measured using flow cytometry.. EPO treatment decreased hypoxia-induced HIF-1alpha protein levels and VEGF transcription, with no effect on cell growth. Inhibition of HIF-1alpha signaling by EPO was also observed in MCF-7 breast cancer cells.. These novel findings suggest that EPO may exhibit anti-angiogenic properties, thus encouraging further exploration of signaling pathways between EPO and HIF-1alpha.

Topics: Cell Growth Processes; Cell Hypoxia; Cell Line, Tumor; Erythropoietin; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Neovascularization, Pathologic; Ovarian Neoplasms; Receptors, Erythropoietin; Recombinant Proteins; RNA, Messenger; Signal Transduction; Transcription, Genetic; Vascular Endothelial Growth Factor A

Topics: Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Confidence Intervals; Disease Progression; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Odds Ratio; Ovarian Neoplasms; Prostatic Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Analysis; Therapeutic Equivalency; Treatment Outcome

We examined whether women aged 60 years or older with ovarian cancer who were treated with surgery and postoperative chemotherapy are at higher risk of developing grade 4 hematological toxicity. Seventy-five patients were included: 34 patients aged < 60 years (group I) were compared with 41 patients aged > or =60 years (group II) after postoperative treatment with single-agent carboplatin or carboplatin/taxane combination chemotherapy. Secondary prophylaxis with granulocyte colony-stimulating factors was performed to avoid dose reduction and chemotherapy delay. A total of 450 chemotherapy cycles was completed. Anemia and thrombocytopenia were mild in both groups. Overall, grade 4 neutropenia developed in 41% (group I) and in 49% (group II) (p=0.51). Febrile neutropenia occurred in 12% and 2%, respectively (p=0.17). The carboplatin/taxane combination was associated with grade 4 neutropenia in 42% (group I) and 58% (group II) (p=0.21). Women > or =60 years are not at higher risk of developing severe myelotoxicity than their younger counterparts, particularly after treatment with carboplatin/taxane combination chemotherapy.

Topics: Adult; Age Factors; Aged; Anemia; Antineoplastic Agents; Carboplatin; Drug Therapy, Combination; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Humans; Middle Aged; Neutropenia; Ovarian Neoplasms; Postoperative Complications; Recombinant Proteins; Retrospective Studies; Risk Factors; Taxoids; Thrombocytopenia

Six hours after an uncomplicated extended resection of ovarian cancer, postoperative arterial bleeding led to life-threatening blood loss in a 44-yr-old Jehovah's Witness who refused blood transfusion. Haemoglobin (Hb) decreased from 2.5 g dl(-1) directly after the emergency laparotomy, followed by a 10 h immeasurable period (below detectable minimum value of the analyser), to a measurable minimum of 1.5 g dl(-1) after 20 h. Haematopoiesis was induced by high-dose i.v. erythropoietin therapy (600 IU kg(-1)) and continued on days 3, 6, 8, 10 and 13. Iron, folic acid and vitamins were given as supplements. The patient needed ventilatory assistance for 18 days and some inotropic support. Complications included increases in pancreatic enzymes and liver enzymes, jaundice and skin necrosis at the fingertips and toes. Myopathy led to transient tetraparesis. Haemoglobin rose from 1.5 to 3.4 g dl(-1) (day 10) and the patient was discharged from the intensive care unit with haemoglobin 6.5 g dl(-1) on day 24. She made a full recovery and is still free of cancer in remission.

Topics: Adult; Blood Transfusion; Contraindications; Erythropoietin; Female; Humans; Jehovah's Witnesses; Ovarian Neoplasms; Postoperative Hemorrhage; Recombinant Proteins

To assess physician use of erythropoietin in cancer patients before publication of the American Society of Clinical Oncology/American Society of Hematology guidelines.. Questionnaires about erythropoietin use in practice and 12 hypothetical clinical scenarios involving patients with cancer were mailed to 2000 oncologists/hematologists in the United States and 19 other countries. Response rates were 30% in the United States and 25% internationally. Data on erythropoietin use for ovarian cancer were obtained from one clinical trial. Multivariate regression models assessed predictors of erythropoietin prescription.. Most physicians selected a hemoglobin level < or =10 g/dL as an upper threshold for erythropoietin use (36% to 51% of U.S. physicians and 21% to 32% of foreign physicians). Frequent erythropoietin use (defined as use in at least 10% of cancer patients) was higher in the United States than elsewhere (adjusted odds ratio [OR] = 5.8; 95% confidence interval [CI]: 2.5 to 13.4). Among U.S. physicians, those who said they used erythropoietin frequently were more likely to be in fee-for-service than managed care settings (OR = 2.2; 95% CI: 1.3 to 3.7). Those who reported never using erythropoietin practiced in countries that had lower annual per capita health care expenditures, lower proportions of privately funded health care, and a national health service (P <0.05 for all comparisons). Of 235 ovarian cancer patients who received topotecan, 38% (45/118) of U.S. patients and 2% (2/117) of European patients who developed grade 1 anemia (hemoglobin level between 10 and 12 g/dL) were treated with erythropoietin (P <0.01).. Financial considerations and a hemoglobin level <10 g/dL appear to influence erythropoietin use in the United States, whereas financial considerations alone determine erythropoietin use abroad.

Topics: Anemia; Antineoplastic Agents; Confidence Intervals; Cost Savings; Cross-Cultural Comparison; Drug Utilization; Erythropoietin; Fee-for-Service Plans; Female; Health Expenditures; Hemoglobinometry; Humans; Male; Managed Care Programs; Medical Oncology; Neoplasms; Odds Ratio; Ovarian Neoplasms; Practice Guidelines as Topic; Practice Patterns, Physicians'; Regression Analysis; Topotecan; United States

The purpose of this study was to investigate the possible benefit of the paclitaxel based combined chemotherapy introduced as an "up front" chemotherapy in Hungary for the treatment of ovary cancer.. Data of four Hungarian Ovary Cancer Treatment Center was collected, evaluated and presented here as a preliminary retrospective study. Data of 67 patients was included into the investigation who underwent laparatomy followed with paclitaxel/carboplatin or paclitaxel/cisplatin combined chemotherapy between 1st of July 1999 and 31st of December 2000. The paclitaxel was administered as 135 mg/m2 i.v. infusion for 3 hours. The main attention was pay on the response rate and the side effect occurred during the administration of the anticancer drugs.. 34 out of 67 patients underwent optimal surgery, and 33 out of 67 had got suboptimal procedure only. The chemotherapy was started at the 7th postoperative day. 430 cycles of chemotherapy was evaluated. The overall response rate (RR) at the end of the treatment was 76.1% (CR 68.65%. PR 7.46%). At the end of the follow-up there was 41 patients free of disease (61.19%), 12 patients alive with residual disease (17.91%), 10 patients (14.9%) died of disease, and there was 4 (6%) patients lost. The overall survival (OS) during the follow up period was 16.82 months. In the suboptimally operated group, 36.3% of the patients (12/33) underwent second laparotomy after the 3rd cycle of chemotherapy. Optimal operation was done in 8 out of this 12 patients and all of optimally operated patients remained free of disease at the and of the follow up. Three treatment out of 67 was interrupted because of major side effect, and 13 patients needed supportive treatment. Eleven blood transfusions was performed during the chemotherapy and erythropoetin (EPO) was administered in two patients.. The outcome of patients during of follow up period was better in the optimally operated group. There was 2 death compared to 8 in suboptimally operated group, the progression free survival (PFS) was longer (8 vs. 6.54 months), and so was the OS (17.11 vs. 16.54 months). More disease free patients was registered at the end of follow-up in the optimally operated group (29 vs. 12). The haematological side effect was also more frequent in the suboptimally operated group (12 vs 1). The data suggest that the quality of initial surgical procedure remains the main prognostic factor even if paclitaxel based combine chemotherapy is administered. On the other hand due to the paclitaxel based chemotherapy seems to be a promising "up front" treatment in patients with ovary cancer with few major side effect generally, and quite a lot haematological side effect in the suboptimally operated group only.

Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Carboplatin; Carcinoma; Chemotherapy, Adjuvant; Cisplatin; Disease Progression; Drug Administration Schedule; Erythropoietin; Female; Humans; Hungary; Middle Aged; Neoplasm, Residual; Ovarian Neoplasms; Paclitaxel; Registries; Retrospective Studies; Survival Analysis; Treatment Outcome

Anemia is a common complication of cancer that has been associated with poor response to treatment and decreased survival in many malignancies. A retrospective chart review was undertaken to determine the effects of hemoglobin (Hb) levels, measured prior to initiation of chemotherapy and before each chemotherapy cycle, and clinical prognostic factors (e.g., age, tumor stage, residual tumor size, hematologic parameters, and type of health insurance) in 250 ovarian cancer patients treated between 1985 and 1998. All patients were scheduled to receive at least 6 courses of systemic chemotherapy. None of the patients received recombinant human erythropoietin. The difference between observed overall survival and its predicted value was computed by multiple regression analysis for each patient with respect to prognostic factors. Hemoglobin levels prior to and during chemotherapy were identified as a prognostic factor for overall survival. Hemoglobin levels > or =12 g/dl were significantly associated with prolonged overall survival (P<0.001). In addition, Hb level correlated with scheduled completion of chemotherapy, overall therapeutic success, tumor stage, age at diagnosis, and residual tumor size (all, P<0.005). Hemoglobin level represents an important prognostic factor for patients with ovarian cancer. This finding supports the use of measures to maintain adequate Hb levels, such as treatment with recombinant human erythropoietin, to improve patient survival.

Topics: Adult; Antineoplastic Agents; Erythropoietin; Female; Hemoglobins; Humans; Middle Aged; Multivariate Analysis; Ovarian Neoplasms; Oxygen; Prognosis; Proportional Hazards Models; Recombinant Proteins; Time Factors

Topics: Anemia; Erythropoietin; Female; Hemoglobins; Humans; Ovarian Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

We have recently shown that malignant tumours from the ovary and uterus expressed erythropoietin (Epo) and its receptor (EpoR), and that deprivation of Epo signal in tumour blocks induced death of malignant cells and capillary endothelial cells in vitro (Yasuda et al, submitted). These in vitro results prompted us to examine the effect of Epo-signal withdrawal on tumours in vivo. RT-PCR analysis demonstrated the expression of mRNAs for Epo and EpoR in the transplants of uterine and ovarian tumours in nude mice. Then we injected locally anti-Epo antibody or soluble form of EpoR into the transplants. At 12 h, 1, 7 or 14 days after the injection, all transplants were resected and examined macro- and microscopically. Tumour size was reduced in Epo signal-deprived transplants. Immunohistochemical examinations revealed destruction of Epo-responding malignant and capillary endothelial cells through apoptotic death. The degree of tumour regression correlated well with the dose and frequency of the injections. Control xenografts with saline injection or needle insertion showed well-developed tumour masses. This Epo response pathway will have profound implications for our understanding of the development and progression of malignant tumours and for the use of Epo-signal deprivation as an effective therapy.

Topics: Animals; Cell Division; Erythropoietin; Female; Immunohistochemistry; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Pathologic; Ovarian Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Transplantation, Heterologous; Uterine Neoplasms

To investigate the effects of repeated cis-dichlorodiamine-platinum (CDDP) exposure on serum erythropoietin (Epo) levels.. In seven patients with ovarian cancer, Epo and haemoglobin concentration (c(Hb)) were measured before, 24h and 7 days after administration of the first three courses of chemotherapy. In seven control patients undergoing gynaecological surgery for non-malignant reasons, Epo and c(Hb) were measured before, 24h and 7 days after the operation.. Following Epo increased, independent of concomitant anaemia, especially after the third course: 51mU/ml (S.D. 46) versus 122mU/ml (S.D. 83) (P=0.02). In the control patients, Epo was lower although the decrease of c(Hb) was significantly higher.. Cis-platinum chemotherapy induces an increase in erythropoietin levels independent of anaemia. The underlying mechanism remains to be investigated.

Topics: Aged; Anemia; Antineoplastic Agents; Cisplatin; Erythropoietin; Female; Hemoglobins; Humans; Middle Aged; Ovarian Neoplasms; Prospective Studies

A fusion protein made of human granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO), referred to as MEN 11303, has been tested for biologic activity using mobilized CD34(+) cells.. MEN 11303 and a combination of GM-CSF/EPO produced the same amount of colony-forming unit granulocyte-macrophage (CFU-GM), of burst-forming unit erythroid (BFU-E), and of multipotent CFU-mixed. After 15 days, liquid cultures of CD34(+) cells exposed to MEN 11303 yielded a total cell number larger than that obtained with an equimolar mixture of GM-CSF and EPO, with a clear prevalence of cells exhibiting an erythroid phenotype. A colony-forming cell assay established from CD34(+) cells precultured with MEN 11303 for 7 days yielded a greater amount of BFU-E than GM-CSF/EPO combination. Exposing CD34(+) cells to MEN 11303 for 7 days in liquid culture resulted in higher recoveries of cells expressing a comparatively less differentiated hematopoietic phenotype and of long-term culture initiating cells. A cell-based binding-competition assay using the human EPO-receptor (EPO-R) transfected murine Ba/F3EPOR cell line showed that MEN 11303 bound to EPO-R with a sixfold lower affinity but induced a more sustained receptor phosphorylation. MEN 11303 supported the growth of Ba/F3EPOR cells more efficiently than EPO and remained detectable in the spent culture medium for a longer time.. MEN 11303 and the combination of GM-CSF/EPO are equally potent in recruiting hematopoietic progenitors into cycle, but the fusion protein is superior in promoting the expansion of committed erythroid percursors. Primitive hematopoiesis is less affected by MEN110303 than GM-CSF/EPO combination. Part of these effects may reflect the peculiar interaction of the EPO moiety of MEN 11303 with the EPO-R.

Topics: Antigens, CD34; Breast Neoplasms; Cell Differentiation; Cells, Cultured; Colony-Forming Units Assay; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; Immunophenotyping; Membrane Glycoproteins; Ovarian Neoplasms; Phenotype; Phosphorylation; Receptors, Immunologic; Sialic Acid Binding Ig-like Lectin 1

Ex vivo stroma-free static liquid cultures of granulocyte colony-stimulating factor (G-CSF)/chemotherapy-mobilized CD34+ cells were established from patients with epithelial solid tumors. Different culture conditions were generated by adding G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), Flt3 ligand (Flt3), megakaryocyte growth and development factor (Peg-rHuMGDF), GM-CSF/erythropoietin (EPO) hybrid protein (MEN11303), and interleukin-15 (IL-15) to the basic stem cell factor (SCF) + interleukin-3 (IL-3) + EPO combination. This study showed that, among the nine different combinations tested in our 5% autologous plasma-containing cultures, only those containing IL-3/SCF/Flt3/MEN11303 and IL-3/SCF/Flt3/MEN11303/IL-15 significantly expanded colony-forming unit granulocyte-macrophage (CFU-GM), burst-forming unit erythroid (BFU-E), long-term culture-initiating cells (LTC-IC), CD34+, and CD34+/CD38- cells after 14 days of culture. Particularly, the addition of IL-15 to IL-3/SCF/Flt3/MEN11303 combination produced a significant increase of LTC-IC, with an average 26-fold amplification as compared to input cells, without any detrimental effect on CFU-GM and BFU-E expansion. This combination also produced a statistically significant 3.6-fold expansion of primitive CD34+/CD38- cells. Moreover, this study confirms the previously described erythropoietic effect of MEN11303, which, in our experience, was the only factor capable of expanding BFU-E. Compared to equimolar concentrations of GM-CSF and EPO, MEN11303 hybrid protein showed a significantly higher capacity of expanding CFU-GM, BFU-E, LTC-IC, CD34+, and CD34+/CD38- cells when these cytokines were tested in combination with IL-3/SCF/Flt3. These cultures indicated that Peg-rHuMGDF addition to IL-3/SCF/EPO/Flt3 does not affect CFU-GM and BFU-E expansion but, unlike G-CSF or GM-CSF, it does not decrease the ability of Flt3 to expand primitive LTC-IC. These studies indicate that, starting from G-CSF/chemotherapy-mobilized CD34+ cells, concomitant expansion of primitive LTC-IC, CFU-GM, BFU-E, CD34+, and CD34+/CD38- cells is feasible in simple stroma-free static liquid cultures, provided IL-3/SCF/Flt3/MEN11303/IL-15 combination is used as expanding cocktail in the presence of 5% autologous plasma.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cells, Cultured; Colony-Forming Units Assay; Erythropoiesis; Erythropoietin; Female; fms-Like Tyrosine Kinase 3; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Humans; Interleukin-15; Middle Aged; Ovarian Neoplasms; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases

Experiments were designed to evaluate the effect of an elevated hematocrit using recombinant human erythropoietin (Epo) on the antitumor response of cisplatin on human ovarian cancer engrafted in mice.. Forty female severe combined immunodeficient (SCID) mice with large human ovarian cancer xenografts implanted on the gonadal fat pad (GFP) and 40 female SCID mice with small subcutaneous (sq) human ovarian cancer xenografts were placed in one of four treatment groups. Group 1 (controls) received phosphate-buffered saline injections. Group 2 (Epo group) received Epo at 20 units three times per week. Group 3 (cisplatin group) received cisplatin at 5 mg/kg/week. Group 4 (Epo + cisplatin group) received Epo and cisplatin as above. Cisplatin was administered on day 0 for mice bearing large GFP tumors and was injected on days 0 and +7 for mice bearing small sq tumors. Epo injections were started on day -15 and continued until the completion of the experiment. Evaluations of the tumor growth, hematocrits, and performance status were made. The experiments were repeated in 24 SCID mice bearing small sq tumor xenografts with similar results. Representative data were reported.. Among mice bearing large GFP tumors, a tumor growth delay was noted in the groups that received cisplatin with or without Epo compared to controls (P < 0.05). However, significant tumor growth delay could not be reached for mice in the Epo + cisplatin group compared to the cisplatin group (P = 0.07). Among mice bearing small sq tumors, a significant improvement in tumor regression was achieved in the Epo + cisplatin group compared to the cisplatin group (P < 0.05). No difference in tumor growth resulted in the Epo group compared to controls. Epo resulted in a 25-35% increase in the hematocrit in both the Epo group and the Epo + cisplatin group (P < 0.01). Mice in the control and in the Epo groups remained healthy. Mice treated with cisplatin developed objective signs of morbidity; however, performance scores for mice in the Epo + cisplatin group remained lower than scores in the cisplatin group.. The data demonstrate a cisplatin-sensitizing effect on human ovarian cancer in SCID mice induced by the pretreatment elevation and maintenance of the hematocrit using Epo. These findings are consistent with an oxygen sensitization of cisplatin. Corroboration of these results may have significant clinical implications for the treatment of solid tumor patients.

Topics: Animals; Antineoplastic Agents; Cisplatin; Drug Interactions; Erythropoietin; Female; Humans; Mice; Mice, SCID; Neoplasm Transplantation; Ovarian Neoplasms; Oxygen; Recombinant Proteins

Advanced cancer is commonly associated with significant anemia which worsens with the administration of cytotoxic drugs. Erythropoietin (EPO) levels in these patients are usually inappropriately low for the degree of anemia. We evaluated the effect of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) on hematologic parameters and transfusion requirements in anemic cancer patients who were receiving platinum-based chemotherapy. Baseline studies included complete hemogram, reticulocyte count, serum iron, TIBC, ferritin and determination of performance status and quality of life (QOL). Twenty-three patients, 13 females, 10 males with mean age 52 years received 150 units/kg of r-HuEPO three times weekly for a minimum of 10 weeks. They also received supplemental iron. Ovarian cancer was the commonest underlying malignancy. Most of the patients received platinum-based combination chemotherapy. Mean duration of r-HuEPO therapy was 12.6 weeks. Average baseline reticulocyte count was 1.8% which increased to 7.0% after one week therapy. Eight patients had normalization of hemoglobin values. Another eight patients improved their hemoglobin by at least 2 g/dl, however, hemoglobin values remained below the normal range. Two patients had only slight increase in hemoglobin but never required blood transfusion. Three patients who were transfusion dependent had decrease in the transfusion requirements. Two patients had no significant benefit. In most patients response was evident within 2 weeks. All responders had improvement in QOL. No significant toxicity was observed. We conclude that r-HuEPO, given subcutaneously, is highly effective in amelioration of anemia and prevention of or reduction in transfusion requirements in cancer patients receiving platinum-based chemotherapy.

Topics: Activities of Daily Living; Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cisplatin; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Injections, Subcutaneous; Iron; Lung Neoplasms; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Quality of Life; Recombinant Proteins; Reticulocyte Count

A combination of erythropoietin (EPO) plus stem cell factor (SCF) drove purified unfractionated granulocyte colony stimulating factor (G-CSF)/chemotherapy mobilized peripheral blood CD34+ cells to selective erythroid differentiation in liquid culture with an average 28-fold increase in the total cell number after 21 d. From day 6 of culture cytologic and cytofluorimetric characterization revealed that cultured cells belonged to the erythroid lineage with a gradual wave of maturation along the erythroid pathway to terminal cells. A similar pattern of erythroid differentiation was observed when the same peripheral blood CD34+ cells were culture with EPO plus SCF in serum-free medium. This cytokine combination produced selective erythroid differentiation with the complete exhaustion of the clonogenic potential on day 21. In parallel experiments the same circulating CD34+ cells underwent granulocytic/ monocytic differentiation in liquid culture in response to granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-3 (IL-3) and SCF, demonstrating that these CD34+ progenitors had intact pluripotent differentiating potential. Conversely, bone marrow CD34+ cells isolated from bone marrow allografts were unable to selectively differentiate along the erythroid pathway when they were exposed to EPO plus SCF combination. However, these cells maintained a greater number of colony forming cells on day 21 of culture compared to mobilized peripheral blood CD34+ cells. This model is a simple and reliable way to obtain selective erythroid differentiation of peripheral blood G-CSF/ chemotherapy mobilized CD34+ progenitor cells in liquid culture. The absence of cytokines such as GM-CSF and IL-3 in the culture medium permits studies on in vitro erythropoiesis without disturbance of prevalent myelopoiesis.

Topics: Antigens, CD34; Bone Marrow; Cell Differentiation; Cell Lineage; Cells, Cultured; Erythroid Precursor Cells; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Humans; Ovarian Neoplasms; Stem Cell Factor

The plasma concentrations of erythropoietin (Ep), soluble transferrin receptors (sTfRs), iron, total iron binding capacity (TIBC) and ferritin were monitored in five leukaemia patients undergoing autologous bone marrow stem cell transplantation (BMSCT) and in 10 lymphoma and 21 ovarian cancer patients undergoing autologous peripheral blood SCT (PBSCT); 9/21 ovarian cancer patients received recombinant human G-CSF and Ep and six recombinant human GM-CSF and Ep following SCT. All parameters were evaluated in relation to the kinetics of erythroid reconstitution as evaluated by haemoglobin (Hb) and reticulocyte levels [including the fraction of immature reticulocytes, also called highly fluorescent reticulocytes (HFR)]. Leukaemia patients undergoing BMSCT showed only a delayed (occurring at days 35-50 after SCT) and partial RBC, neutrophil and platelet recovery, whereas all patients undergoing PBSCT exhibited a rapid (occurring at days 10-15 after SCT) and sustained haemopoietic recovery. The various levels of erythroid rescue observed among these patients markedly influenced the kinetics of the different parameters investigated: (i) in leukaemia BMSCT patients sTfRs declined following SCT and remained at low levels thereafter, whereas Ep, iron. TIBC and ferritin showed a progressive and significant increase; (ii) in the different groups of patients undergoing PBSCT: (a) sTfR levels first declined following SCT and then returned to pre-therapy values at days 12-16, this response preceded erythropoietic recovery; (b) Ep, total iron, TIBC and ferritin showed an initial increase in the first days following SCT and then returned to pre-therapy values. Altogether, these observations indicate that: (i) both sTfR levels and reticulocyte counts are predictive parameters of erythropoietic recovery; (ii) coordinated changes of biochemical parameters underlying iron metabolism (iron, TIBC and ferritin) accompany erythroid rescue following SCT.

Topics: Adolescent; Adult; Aged; Erythropoiesis; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hemoglobins; Humans; Leukemia; Lymphoma; Male; Middle Aged; Ovarian Neoplasms; Receptors, Transferrin; Reticulocyte Count

To apply recombinant human (rh)erythropoietin (EPO) to predeposit autologous blood donation (P.A.B.D.) in cancer patients clinically, (1) we tested the effects of rh-EPO on 2 ovarian cancer cell lines in vitro at first, then, (2) studied the effect of the rh-EPO for switch back (SB) method that is a variant of P.A.B.D. clinically. Rh-EPO (0.068-68U/ml) caused no significant and reproducible stimulation of clonal growth to SHIN-3 (derived from serous cyst adenocarcinoma) and MN-1 (derived from mucinous cyst adenocarcinoma). Twenty-five cases were studied. The change in the hemoglobin concentration (delta Hb) was -0.43 +/- 1.38g/dl (mean +/- SD) and the change in the total amount of hemoglobin (total delta Hb) which is calculated on the basis of whole blood volume was 111.5 +/- 53.2g/body in 16 cases with rh-EPO. The delta Hb and total delta Hb were -3.25 +/- 0.78g/dl and 30.1 +/- 41.7g/body in 9 cases without rh-EPO. The rh-EPO combined cases were significantly increased in both delta Hb and total delta Hb (p < 0.05, unpaired student t test). We therefore conclude that it would be very beneficial to use rh-EPO combined with the SB method in P.A.B.D. for high maximum surgical blood order schedule (MSBOS) cases such as gynecological malignancies.

Topics: Adult; Aged; Blood Transfusion, Autologous; Cell Division; Cystadenocarcinoma, Mucinous; Cystadenocarcinoma, Serous; Erythropoietin; Female; Genital Neoplasms, Female; Humans; Middle Aged; Ovarian Neoplasms; Recombinant Proteins; Tumor Cells, Cultured

We have reviewed the incidence of cisplatin-induced anaemia in patients affected with solid tumours treated with at least three courses of first-line cisplatin-containing regimens. In our experience, a low percentage (5%) of patients required transfusions of red blood cells. We think it is of the utmost importance to adopt uniform criteria in monitoring and treatment of patients at risk of developing cisplatin anaemia and to identify subsets of patients to eventually treat with erythropoietin.

Topics: Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Erythrocyte Transfusion; Erythropoietin; Evaluation Studies as Topic; Female; Humans; Incidence; Lung Neoplasms; Male; Ovarian Neoplasms; Prostatic Neoplasms; Retrospective Studies; Risk Factors

Cisplatin-based therapy results in a cumulative anemia that is disproportionate to the effects on other blood cells. The severity of this treatment-induced anemia and the resultant transfusion requirement in cancer patients correlate with cisplatin-induced renal tubular dysfunction. Observed/expected serum erythropoietin (EPO) ratios decline with progressive cisplatin therapy and are proportionate to the degree of renal dysfunction. Recovery from anemia and of observed/expected serum EPO ratios in patients occurs after cessation of cisplatin therapy, along with restoration of renal tubular function. Creatinine clearance, however, remains permanently depressed. Cisplatin-treated rats develop progressive renal dysfunction and anemia that persists for many weeks, without effects on white blood cell counts. The anemia is also associated with a lack of expected EPO and reticulocyte response. With EPO administration, cisplatin-treated rats exhibit a greater reticulocyte response and hematocrit increment then non-cisplatin-treated rats given EPO, indicating minimal erythroid precursor cell damage from cisplatin. These results indicate the primary etiology of cisplatin-associated anemia is a transient, but persisting EPO deficiency state resulting from cisplatin-induced renal tubular damage, which can be prevented or treated by hormone (EPO) replacement.

Topics: Aged; Aged, 80 and over; Anemia; Animals; Blood Cell Count; Bone Marrow; Cisplatin; Creatinine; Doxorubicin; Erythropoietin; Female; Follow-Up Studies; Hematocrit; Humans; Kidney Function Tests; Kidney Tubules; Magnesium; Male; Middle Aged; Multivariate Analysis; Ovarian Neoplasms; Phenylhydrazines; Rats; Syndrome; Urinary Bladder Neoplasms

We tested in vitro the effect of recombinant human erythropoietin (rhEPO) plus recombinant human G-CSF (rhG-CSF) on purified human CD34+ haemopoietic progenitors (HP) and in vivo in patients who had undergone anti-cancer chemotherapy for advanced ovarian cancer. In this preliminary experience we found that, in vitro, rhEPO potentiates the effect of rhG-CSF on HP growth and differentiation toward the granulocyte-macrophage lineage. rhEPO plus rhG-CSF produced in vitro a proliferative stimulus of HP which represents 26% of the maximum stimulation obtained using IL-1, IL-3, IL-6, G-CSF, GM-CSF and stem cell factor in combination. In the patients treated with rhEPO plus rhG-CSF after chemotherapy, we observed a favourable trend for platelet and neutrophil recoveries compared with a control group treated with rhG-CSF alone and a significantly higher haematocrit nadir was observed in the rhEPO plus rhG-CSF series. In the patients treated with rhEPO plus rhG-CSF we observed a significant increase of circulating colony-forming unit granulocyte-macrophage (CFU-GM) and burst forming unit-erythroid (BFU-e) compared with the rhG-CSF series. Our results, in vitro and in vivo, encourage the in vivo use of rhEPO plus rhG-CSF to improve blood cell recoveries of patients who have undergone conventional or high-dose chemotherapy. Moreover, rhEPO plus rhG-CSF was demonstrated to be a good HP mobilising treatment for blood stem cell collection after chemotherapy.

Topics: Adult; Antineoplastic Agents; Blood Cell Count; Cell Differentiation; Cell Division; Colony-Forming Units Assay; Drug Synergism; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; In Vitro Techniques; Middle Aged; Ovarian Neoplasms; Recombinant Proteins

Serum immunoerythropoietin (SIE) levels were studied of 25 randomly chosen cancer patients undergoing cisplatin-based chemotherapy and ten head and neck cancer patients who were studied prospectively before and during cisplatin-based therapy. The SIE levels were determined by standard radioimmunoassay, and the results were interpreted relative to erythropoietin levels and hematocrits of 17 aplastic or nutritionally anemic patients who were believed to have a normal erythropoietin response. Of the 25 randomly chosen patients, SIE levels were inappropriately low in four patients. In this population, there was a greater likelihood of erythropoietin deficiency in the patients with a hematocrit less than 30% compared with those with higher values (P less than 0.001), although there was no correlation between SIE level and the amount of cisplatin these patients received or their degree of renal impairment. Of the ten head and neck cancer patients, five were found to have inappropriately low SIE levels before therapy, and two additional patients had a decrease of SIE levels during therapy, in one patient to an abnormally low level. The anemia associated with malignancy was concluded to be in part associated with a relative erythropoietin deficiency, and in certain individuals, cisplatin therapy may contribute to that deficiency.

Topics: Adult; Aged; Anemia; Carcinoma, Non-Small-Cell Lung; Cisplatin; Cohort Studies; Erythropoietin; Female; Head and Neck Neoplasms; Hematocrit; Humans; Lung Neoplasms; Lymphoma; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Prospective Studies

Paraneoplastic erythrocytosis associated with production of erythropoietin and testosterone by a malignant lipid cell tumor is demonstrated in this case report. Several chemotherapeutic regimens failed to halt the progression of this aggressive metastatic lipid cell tumor. The scant literature on malignant lipid cell tumors is reviewed. Possible mechanisms for paraneoplastic erythrocytosis are presented. Adequate control of polycythemia preoperatively will reduce thromboembolic and hemorrhagic complications.

Topics: Combined Modality Therapy; Erythropoietin; Female; Humans; Hysterectomy; Laparotomy; Leydig Cell Tumor; Middle Aged; Neoplasm Metastasis; Ovarian Neoplasms; Paraneoplastic Endocrine Syndromes; Polycythemia; Progesterone; Sex Characteristics; Testosterone; Virilism

A patient with dermoid cyst of the ovary and erythrocytosis is described. Surgical removal of the tumour was followed by a progressive decrease of the red cell mass with remission of the haematological abnormalities. Tumor fluid contained significant erythropoietic stimulating activity. This seems to be the first documented case of erythrocytosis associated with ovarian cyst.

Topics: Aged; Dermoid Cyst; Erythropoiesis; Erythropoietin; Female; Humans; Ovarian Neoplasms; Polycythemia

Topics: Anemia, Hemolytic, Autoimmune; Autoantibodies; Complement System Proteins; Erythropoietin; Female; Heart; Hemolysis; Humans; In Vitro Techniques; Insulin Antibodies; Ovarian Neoplasms