scholarly journals Effects of interleukin-3 after chemotherapy for advanced ovarian cancer

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1141-1148
Author(s):  
B Biesma ◽  
PH Willemse ◽  
NH Mulder ◽  
DT Sleijfer ◽  
JA Gietema ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Side Effects ◽  
Plasma Levels ◽  
Liver Toxicity ◽  
Advanced Ovarian Cancer ◽  
Maximum Tolerated Dose ◽  
Necrosis Factor Alpha ◽  
Interleukin 3 ◽  
Amyloid A ◽  
Facial Erythema

To define the maximum tolerated dose and to study whether recombinant human interleukin-3 (rhIL-3) reduced chemotherapy-induced neutropenia and thrombocytopenia, 20 chemotherapy-naive patients with advanced ovarian cancer eligible for treatment with 6 cycles of carboplatin- cyclophosphamide every 4 weeks (day 1) were entered in a phase I/II open, single-center trial. Cohorts of five patients received during 7 days 1, 5, 10, or 15 micrograms/kg/d rhIL-3 (days 5 through 11) in cycles 1, 3, and 5 by continuous intravenous (IV) infusion or once daily subcutaneous (SC) administration. In control cycles 2, 4, and 6, no rhIL-3 was administered. rhIL-3 significantly increased the recovery of leukocyte, neutrophil, and platelet counts, especially at 5, 10, and 15 micrograms/kg rhIL-3. rhIL-3 also increased basophil, eosinophil, monocyte, and lymphocyte counts at this dose steps. Effects on reticulocytes were limited. No difference in efficacy between SC and IV rhIL-3 treatment was found. Chemotherapy postponement for insufficient bone marrow recovery was necessary in 22 of 45 control cycles versus 2 of 49 rhIL-3 cycles (P less than .001). Platelet transfusions were required in 7 of 45 control cycles versus 3 of 50 rhIL-3 cycles (P less than .5). rhIL-3 up to 10 micrograms/kg/d could be administered without severe side effects. At 15 micrograms/kg/d, rhIL-3 headache was dose- limiting. Other side effects were fever, flu-like symptoms, nausea, skin rash, flushing, facial erythema, and urticaria. Liver toxicity occurred in rhIL-3 and control cycles. rhIL-3 slightly increased tumor necrosis factor alpha, C-reactive protein, and serum amyloid A plasma levels, whereas no effect on IL-6 plasma levels was observed. rhIL-3 administered SC appears to be an interesting hematopoietic growth factor for reduction of chemotherapy-induced myelotoxicity.

scholarly journals Effects of interleukin-3 after chemotherapy for advanced ovarian cancer

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1141-1148 ◽  
Author(s):  
B Biesma ◽  
PH Willemse ◽  
NH Mulder ◽  
DT Sleijfer ◽  
JA Gietema ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Side Effects ◽  
Plasma Levels ◽  
Liver Toxicity ◽  
Advanced Ovarian Cancer ◽  
Maximum Tolerated Dose ◽  
Necrosis Factor Alpha ◽  
Interleukin 3 ◽  
Amyloid A ◽  
Facial Erythema

Abstract To define the maximum tolerated dose and to study whether recombinant human interleukin-3 (rhIL-3) reduced chemotherapy-induced neutropenia and thrombocytopenia, 20 chemotherapy-naive patients with advanced ovarian cancer eligible for treatment with 6 cycles of carboplatin- cyclophosphamide every 4 weeks (day 1) were entered in a phase I/II open, single-center trial. Cohorts of five patients received during 7 days 1, 5, 10, or 15 micrograms/kg/d rhIL-3 (days 5 through 11) in cycles 1, 3, and 5 by continuous intravenous (IV) infusion or once daily subcutaneous (SC) administration. In control cycles 2, 4, and 6, no rhIL-3 was administered. rhIL-3 significantly increased the recovery of leukocyte, neutrophil, and platelet counts, especially at 5, 10, and 15 micrograms/kg rhIL-3. rhIL-3 also increased basophil, eosinophil, monocyte, and lymphocyte counts at this dose steps. Effects on reticulocytes were limited. No difference in efficacy between SC and IV rhIL-3 treatment was found. Chemotherapy postponement for insufficient bone marrow recovery was necessary in 22 of 45 control cycles versus 2 of 49 rhIL-3 cycles (P less than .001). Platelet transfusions were required in 7 of 45 control cycles versus 3 of 50 rhIL-3 cycles (P less than .5). rhIL-3 up to 10 micrograms/kg/d could be administered without severe side effects. At 15 micrograms/kg/d, rhIL-3 headache was dose- limiting. Other side effects were fever, flu-like symptoms, nausea, skin rash, flushing, facial erythema, and urticaria. Liver toxicity occurred in rhIL-3 and control cycles. rhIL-3 slightly increased tumor necrosis factor alpha, C-reactive protein, and serum amyloid A plasma levels, whereas no effect on IL-6 plasma levels was observed. rhIL-3 administered SC appears to be an interesting hematopoietic growth factor for reduction of chemotherapy-induced myelotoxicity.

Phase I and pharmacologic study of paclitaxel administered weekly in patients with relapsed ovarian cancer.

1997 ◽  
Vol 15 (1) ◽  
pp. 187-192 ◽  
Author(s):  
D Fennelly ◽  
C Aghajanian ◽  
F Shapiro ◽  
C O'Flaherty ◽  
M McKenzie ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Standard Dose ◽  
Advanced Ovarian Cancer ◽  
Dose Intensity ◽  
Maximum Tolerated Dose ◽  
Significant Activity ◽  
Weekly Schedule ◽  
The Mean

PURPOSE Paclitaxel has shown significant activity in advanced ovarian cancer. In vitro studies with paclitaxel have suggested that fractionated brief infusion schedules may be more effective than the standard 24-hour infusion. We commenced a phase I evaluation of escalating-dose paclitaxel (40, 50, 60, 80, 100 mg/m2) administered weekly as a 1-hour infusion in patients with recurrent ovarian cancer. All patients had received prior paclitaxel and cisplatin therapy. All patients received standard premedication. PATIENTS AND METHODS Eighteen patients are assessable on this phase I study. The mean age was 54 years (range, 48 to 74). The median number of prior chemotherapy regimens was three (range, two to five). The mean paclitaxel-free interval was 10.1 months (range, 1 to 24). RESULTS A total of 194 cycles of therapy were administered, with a mean of 10 (range, one to 12) per patient. No mucositis or grade III neuropathy was seen. Alopecia occurred in one out of 18 assessable patients. The mean neutrophil nadir was 4.0 x 10(9)/L. At the top dose level (100 mg/m2) delivered, dose-intensity was 90.75% of that planned and greater than two fold the standard dose-intensity. Partial responses were seen in four of 13 assessable patients (30%). Two patients with progression of disease on standard three-week paclitaxel schedules switched to a weekly schedule with demonstrated response. Increasing paclitaxel dose correlated with measured area under the curve (AUC) (R2 = .614). Dose-limiting toxicity was reached at 100 mg/m2 with two of three patients experiencing a treatment delay, thus defining a maximum-tolerated dose of 80 mg/m2 in this group of heavily pretreated patients on this weekly schedule. CONCLUSION (1) Paclitaxel administered as a 1-hour infusion is well tolerated; (2) this schedule of administration does not result in cumulative myelosuppression; and (3) this schedule of administration results in dose-intensive paclitaxel delivery with a favorable toxicity profile.

Abstract 3476: Higher plasma levels of heparan sulfate are associated with improved survival of patients with advanced ovarian cancer.

2013 ◽  
Author(s):  
Matthew S. Block ◽  
Matthew J. Maurer ◽  
Krista M. Goergen ◽  
Courtney L. Erskine ◽  
Marshall D. Behrens ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Heparan Sulfate ◽  
Plasma Levels ◽  
Advanced Ovarian Cancer

Phase II Clinical Study on the Effects of Recombinant Human Interleukin-3 on Thrombocytopenia After Chemotherapy for Advanced Ovarian Cancer

1999 ◽  
Vol 22 (6) ◽  
pp. 539-545 ◽  
Author(s):  
Kaichiro Yamamoto ◽  
Akira Yajima ◽  
Yoshiteru Terashima ◽  
Shiro Nozawa ◽  
Yuji Taketani ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Study ◽  
Phase Ii ◽  
Advanced Ovarian Cancer ◽  
Interleukin 3 ◽  
Phase Ii Clinical Study

Weekly and monthly regimens of paclitaxel and carboplatin in the management of advanced ovarian cancer. A preliminary report on side effects

2001 ◽  
Vol 11 (4) ◽  
pp. 295-299 ◽  
Author(s):  
C. H. Wu ◽  
C. H. Yang ◽  
J. N. Lee ◽  
S. C. Hsu ◽  
E. M. Tsai
Keyword(s):  
Ovarian Cancer ◽  
Side Effects ◽  
Preliminary Report ◽  
Advanced Ovarian Cancer ◽  
Hematological Toxicity ◽  
Delayed Treatment ◽  
Significant Difference ◽  
Preliminary Study ◽  
Grade 3 ◽  
Carboplatin Auc

Abstract.Wu CH, Yang CH, Lee JN, Hsu SC, Tsai EM. Weekly and monthly regimens of paclitaxel and carboplatin in the management of advanced ovarian cancer. A preliminary report on side effects.This preliminary study was carried out over 18 months to evaluate whether the side effects in patients with advanced ovarian cancer receiving chemotherapy using paclitaxel-carboplatin differed between weekly (98 cycles in 14 patients) and monthly (102 cycles in 15 patients) administrations. We used paclitaxel (60 mg/m2) and carboplatin (AUC of 2) in the weekly regimen and 175 mg/m2 of paclitaxel and carboplatin (AUC of 6) in the monthly regimen. All eligible patients received at least four cycles of treatment in both regimens. The results revealed significantly decreased hematological toxicity in weekly regimens relative to monthly ones, ie, 7.1% vs. 18.6% of anemia (≥ grade 2), 7.1% vs. 32.3% of grade 3/4 granulocytopenia, and 0% vs. 15.7% of >grade 2 thrombocytopenia. There was no significant difference in nonhematological toxicities between the two regimens. The incidence of unscheduled events was much less in the weekly regimen than in the monthly one; ie, delayed treatment (3 vs. 18 events), unanticipated hospitalizations (3 vs. 15 times), and supplemental support with G-CSF (7 vs. 33 times). Complete responses were observed in 6 of 14 patients in the weekly regimen and in five of 15 patients in the monthly regimen, while partial responses were seen in four and five patients in the weekly and monthly regimens, respectively. The present results demonstrate that the weekly regimen can achieve the benefits of tolerable toxicity with significantly reduced myelosuppression and improved cost-effectiveness in terms of unscheduled events.

Effect of Thio-TEPA on Advanced Ovarian Cancer

1973 ◽  
Vol 59 (4) ◽  
pp. 259-267 ◽  
Author(s):  
Luciano Luciani ◽  
Giuseppe Maria de Palo ◽  
Umberta Conti ◽  
Franco Mattavelli ◽  
Francesco Di Re
Keyword(s):  
Ovarian Cancer ◽  
Side Effects ◽  
Alkylating Agent ◽  
Nitrogen Mustard ◽  
Advanced Disease ◽  
Advanced Ovarian Cancer ◽  
Gastrointestinal Toxicity ◽  
Review Of The Literature ◽  
Therapeutic Value ◽  
Previously Treated

The effect of triethylene thiophosphoramide (Thio-TEPA), an alkylating agent structurally related to nitrogen mustard, has been described in 39 cases of very advanced ovarian carcinoma. Of the 39 cases treated, 21 had been previously treated and 18 were new cases. In the 39 cases, 42 cycles were evaluable (table 1). 8 cases showed a varying degree of improvement. Marked regression of growth and improvement of symptoms (regression exceeding 50%) was achieved in 7 cases (table 1). Regression of less than 50 % was achieved in 1 case (table 1). The clinical regression is only temporary. A high percentage of cases had side-effects. Of the 42 evaluable, 29 (69%) had one or more side-effects; particularly 28 showed leukopenia, 11 trombocytopenia, 13 anemia and 3 oral or gastrointestinal toxicity (table 2). In conclusion the therapeutic value of Thio-TEPA in ovarian cancer is small. A review of the literature has not shown that other drugs offer longer survival. The control of advanced disease can reasonably be more optimistic when randomized, prospective, clinical trials are performed. A plan for investigation in this direction is in preparation.

Phase Ia/Ib trial of bispecific antibody MDX-210 in patients with advanced breast or ovarian cancer that overexpresses the proto-oncogene HER-2/neu.

1995 ◽  
Vol 13 (9) ◽  
pp. 2281-2292 ◽  
Author(s):  
F H Valone ◽  
P A Kaufman ◽  
P M Guyre ◽  
L D Lewis ◽  
V Memoli ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Bispecific Antibody ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Maximum Tolerated Dose ◽  
Advanced Breast ◽  
Type I ◽  
Necrosis Factor Alpha ◽  
Her 2

PURPOSE MDX-210 is a bispecific antibody that binds simultaneously to type I Fc receptors for immunoglobulin G (IgG) (Fc gamma RI) and to the HER-2/neu oncogene protein product. MDX-210 effectively directs Fc gamma RI-positive effector cells such as monocytes and macrophages to phagocytose or kill tumor cells that overexpress HER-2/neu. The goals of this phase Ia/Ib trial were to determine the maximum-tolerated dose (MTD) and/or the optimal biologic dose (OBD) of MDX-210. PATIENTS AND METHODS Patients with advanced breast or ovarian cancer that overexpressed HER-2/neu were eligible for treatment. Cohorts of three patients received a single intravenous (IV) infusion of MDX-210 at increasing dose levels from 0.35 to 10.0 mg/m2. RESULTS Treatment was well tolerated, with most patients experiencing transient grade 1 to 2 fevers, malaise, and hypotension only. Two patients experienced transient grade 3 hypotension at 10.0 mg/m2. Transient monocytopenia and lymphopenia developed at 1 to 2 hours, but no other hematologic changes were observed. Doses of MDX-210 > or = 3.5 mg/m2 saturated > or = 80% of monocyte Fc gamma RI and produced peak plasma concentrations > or = 1 microgram/mL, which is greater than the concentration for optimal monocyte/macrophage activation in vitro. Elevated plasma levels of the monocyte products tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and neopterin were observed with maximal levels at doses > or = 7.0 mg/m2. Localization of MDX-210 in tumor tissue was demonstrated in two patients. One partial and one mixed tumor response were observed among 10 assessable patients. CONCLUSION MDX-210 is immunologically active at well-tolerated doses. The MTD and OBD is 7 to 10 mg/m2.

scholarly journals Blood bioactive sphingolipids in patients with advanced serous epithelial ovarian cancer – mass spectrometry analysis

2021 ◽  
Vol 17 (1) ◽  
pp. 53-61
Author(s):  
Paweł Knapp ◽  
Lubomir Bodnar ◽  
Agnieszka Błachnio-Zabielska ◽  
Joanna Reszeć ◽  
Magdalena Świderska ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Advanced Ovarian Cancer ◽  
Mass Spectrometry Analysis ◽  
Control Group ◽  
Serous Ovarian Cancer ◽  
Figo Staging ◽  
Sphingosine 1 Phosphate ◽  
Bioactive Sphingolipids

IntroductionDue to the lack of highly specific and sensitive methods for diagnosing ovarian cancer at advanced stages (according to the International Federation of Gynecology and Obstetrics (FIGO) classification stage III–IV), new noninvasive biomarkers are urgently needed. This study aims to investigate how the levels of plasma bioactive sphingolipids (ceramides, sphingosine-1-phosphate, sphingosine and sphinganine) are altered in serum, erythrocytes and platelets of patients with advanced serous ovarian cancer.Material and methodsA total of 135 patients with advanced serous ovarian cancer and 159 women with normal ovarian morphology were enrolled. Plasma levels of sphingosine, sphingosine-1-phosphate, sphinganine, ceramide C14:0-Cer, C16:0-Cer, C18:1-Cer, C18:0-Cer, C20:0-Cer, C22:0-Cer, C24:1-Cer and C24:0-Cer were assessed by LC/MS/MS.ResultsPlasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were significantly higher in the advanced ovarian cancer group than in the control group (1.5-fold, p = 0.021; 1.8-fold, p = 0.036 and 1.5-fold, p = 0.031, respectively). Plasma concentration of C18:1-Cer was significantly higher in erythrocytes of women with advanced serous cancer compared to the control group (p = 0.027). Plasma C16-Cer and C18:1-Cer levels and erythrocyte C18:1-Cer levels were able to distinguish patients with moderate/severe serous ovarian cancer from patients with mild ovarian cancer (AUC: 0.86, 0.898, 0.795, respectively). Plasma concentrations of C16, C18.1 and C18 significantly correlated with FIGO staging (p = 0.001, p = 0.024 and p = 0.005), and grading (p = 0.021, p = 0.021 and p = 0.033).ConclusionsPlasma concentrations of C16, C18.1 and C18 correlated with the progression of ovarian cancer (FIGO staging and grading). Plasma levels of C16-Cer and C18:1-Cer and erythrocyte C18:1-Cer levels could be used to distinguish patients with advanced serous ovarian cancer.

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