Oral Medroxyprogesterone Acetate in the Treatment of Advanced or Recurrent Endometrial Carcinoma: A Dose-Response Study by the Gynecologic Oncology Group

1999 ◽  
Vol 17 (6) ◽  
pp. 1736-1736 ◽  
Author(s):  
J. Tate Thigpen ◽  
Mark F. Brady ◽  
Ronald D. Alvarez ◽  
Mark D. Adelson ◽  
Howard D. Homesley ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Endometrial Carcinoma ◽  
Dose Regimen ◽  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
Serum Levels ◽  
High Dose ◽  
High Dose Regimen ◽  
Well Differentiated

PURPOSE: Progestins have definite activity against advanced or recurrent endometrial carcinoma. Both parenteral and oral progestins yield similar serum levels and response rates, which range from 18% to 34%. The one major study that used oral medroxyprogesterone acetate (MPA) noted a response rate at the lower end of the range (18%) and much poorer progression-free and overall survival times (4 and 10.5 months, respectively) than previously reported. The present study sought to confirm this earlier study of oral MPA, to assess the importance of prognostic factors such as histologic grade and receptor levels, and to determine whether a higher dose of MPA would yield a higher response rate. PATIENTS AND METHODS: Two hundred ninety-nine eligible women with advanced or recurrent endometrial carcinoma were randomized to receive oral MPA either 200 mg/d or 1,000 mg/d until unacceptable toxicity intervened or their disease progressed. RESULTS: Among 145 patients receiving the low-dose regimen, there were 25 complete (17%) and 11 partial (8%) responses for an overall response rate of 25%. The 154 patients receiving the high-dose regimen experienced 14 (9%) complete and 10 (6%) partial responses for an overall response rate of 15%. Median durations of progression-free survival were 3.2 months and 2.5 months for the low-dose and high-dose regimens, respectively. Median survival durations were 11.1 months and 7.0 months, respectively. The adjusted relative odds of responding to the high-dose regimen compared with the low-dose regimen was 0.61 (90% confidence interval, 0.36 to 1.04). Prognostic factors having a significant impact on the probability of response included initial performance status, age, histologic grade, and progesterone receptor concentration. Compliance with oral therapy was documented with serum levels 1 month after starting therapy, when possible. MPA levels were commensurate with the assigned dose and schedule. CONCLUSION: Oral MPA is active against endometrial carcinoma. Response to progestin therapy is more frequent among patients with a well-differentiated histology and positive progesterone receptor status. This study provides no evidence to support the use of MPA 1,000 mg/d orally instead of MPA 200 mg/d orally. In fact, the trends suggest the opposite. The use of oral MPA 200 mg/d is a reasonable initial approach to the treatment of advanced or recurrent endometrial carcinoma, particularly those lesions that are well-differentiated and/or progesterone receptor-positive (> 50 fmol/mg cytosol protein). Patients with poorly differentiated and/or progesterone receptor levels less than 50 fmol/mg cytosol protein had only an 8% to 9% response rate.

scholarly journals Effectiveness of low dose versus high dose oxytocin regimen for induction of labour

2021 ◽  
Vol 10 (5) ◽  
pp. 1948
Author(s):  
Paridhi Gupta ◽  
Indu Chawla ◽  
Sonal Gupta
Keyword(s):  
Dose Regimen ◽  
Dose Group ◽  
Low Dose ◽  
Induction Of Labour ◽  
High Dose ◽  
High Dose Regimen ◽  
Nulliparous Women ◽  
Group I ◽  
Significant Difference ◽  
Group Ii

ABSTRACTBackground: Induction of labour is an indispensable part of modern obstetrics and certainly one of the most frequently performed obstetric procedure in the world. Oxytocin, being the most common inducing agent with multiple protocols being practiced, further research is required for the establishment of better protocol with optimal maternal and neonatal outcomes.Methods: Randomized comparative study including 100 term nulliparous women (randomized into high dose, group-I and low dose, group-II with 50 patients in each group) was done. High dose regimen was started with 4mu/min with increment of 4mu/min up to a maximum of 32mu/min and low dose regimen was started with 2mu/min with increment of 2mu/min up to a maximum of 32mu/min. Induction to delivery interval was the primary outcome. Secondary outcomes noted were rate of caesarean section, tachysytole with or without fetal distress, failed induction, maternal outcomes like need for instrumental vaginal delivery, PPH and choriamnionitis, neonatal outcomes like NICU admission, umbilical cord pH and apgar score.Results: There was significant reduction seen in induction to delivery interval among those induced with high dose oxytocin regimen. It was found to be 6.96±3.77 hours in group-I and 9.05±4.65 hours in group-II (p value 0.034). Though incidence of tachysystole was more in high dose regimen, it was not statistically significant. No significant difference was seen in secondary outcomes.Conclusions: On the basis of present study, high dose oxytocin regimen can be considered for induction of labour as it has same effects as that of low dose regimen with lesser induction to delivery interval.

Phase II study of pegylated liposomal doxorubicin (PLD), low-dose dexamethasone (DEX), and lenalidomide (LEN) in patients with newly diagnosed (ND) multiple myeloma (MM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8518-8518
Author(s):  
R. Baz ◽  
M. A. Hussein ◽  
D. Sullivan ◽  
J. Raychaudhuri ◽  
L. Ochoa ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
High Dose ◽  
Hematologic Toxicity ◽  
High Dose Therapy ◽  
Overall Response ◽  
Dose Therapy ◽  
Grade 3

8518 Background: We previously reported the results of a phase I/II trial of PLD, low dose DEX and LEN in patients with relapsed and refractory MM in which the MTD of LEN was 10 mg (for 21 of 28 days) and the overall response rate was 75% with 29% of patients achieving nCR or better (Ann Oncol 2006). Accordingly we evaluated this regimen in ND MM. Methods: We hypothesized that patients with ND MM would tolerate this combination better. Accordingly, patients received PLD (40 mg/m2 on day 1), DEX (40 mg on days 1–4) and LEN (25 mg Days 1–21) every 28 days (for 2 cycles beyond best response: 4–8 cycles). Prophylactic low dose aspirin, acyclovir and fluoroquinolone were recommended. Patients not eligible or not wishing to proceed with high dose therapy continued on the tolerated dose of LEN and DEX until disease progression or unacceptable toxicity. Results: Between 2/2008 and 8/2008, 31 of a planned 60 patients were enrolled. 2 patients were screen failures and are not included in subsequent analysis. The mean age was 64 years (41–82) and 58% were males. The median β2microglobulin was 2.8 mg/dL (34% had β2m>3.5). Using the modified SWOG criteria and after a median of 4 cycles of therapy, the overall response rate was 80% with 40% VGPR and better. Two patients had stable disease and 3 patients had progressive disease. Grade 3/4 hematologic toxicity was as follows: neutropenia (48%), anemia (10%), thrombocytopenia (7%). Grade 3/4 non-hematologic toxicity included: Fatigue (21%), infections and febrile neutropenia (20%, only 1 patient with febrile neutropenia), venous thromboembolic events (10%). 14 patients went off study including 8 patients to proceed with high dose therapy. Conclusions: The combination of PLD, LEN and DEX is an active regimen in patients with ND MM. Due to the unexpected higher rates of neutropenia and fatigue, the dose of PLD will be decreased to 30 mg/m2 every 28 days. Updated results will be presented at the time of the meeting. [Table: see text]

scholarly journals Effects of Shugan-Jianpi Recipe on the Expression of the p38 MAPK/NF-κB Signaling Pathway in the Hepatocytes of NAFLD Rats

Medicines ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. 106 ◽  
Author(s):  
Yuanjun Deng ◽  
Kairui Tang ◽  
Runsen Chen ◽  
Yajie Liu ◽  
Huan Nie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Low Dose ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Model Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α

Background: In traditional Chinese medicine, the Shugan-Jianpi recipe is often used in the treatment of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore the mechanism of the Shugan-Jianpi recipe in relation to rats with NAFLD induced by a high-fat diet. Methods: Rats were randomly divided into eight groups: normal group (NG), model group (MG), low-dose Chaihu–Shugan–San group (L-CG), high-dose Chaihu–Shugan–San group (H-CG), low-dose Shenling–Baizhu–San group (L-SG), high-dose Shenling–Baizhu–San group (H-SG), low dose of integrated-recipes group (L-IG), and high dose of integrated-recipes group (H-IG). After 26 weeks, a lipid profile, aspartate, and alanine aminotransferases in serum were detected. The serum levels of inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using the enzyme linked immunosorbent assay (ELISA) method. Hepatic pathological changes were observed with hematoxylin-eosin (HE) and oil red O staining. The expression of the p38 mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) pathway was detected by quantitative real-time PCR and Western blotting. Results: A pathological section revealed that NAFLD rats have been successfully reproduced. Compared with the model group, each treatment group had different degrees of improvement. The Shugan-Jianpi recipe can inhibit the serum levels of IL-1β, IL-6, and TNF-α in NAFLD rats. The expression of mRNA and a protein related to the p38 MAPK/NF-κB signaling pathway were markedly decreased as a result of the Shugan-Jianpi recipe. Conclusions: The Shugan-Jianpi recipe could attenuate NAFLD progression, and its mechanism may be related to the suppression of the p38 MAPK/NF-κB signaling pathway in hepatocytes.

A randomized trial of standard chemotherapy v a high-dose chemotherapy regimen in the treatment of poor prognosis nonseminomatous germ-cell tumors.

1988 ◽  
Vol 6 (6) ◽  
pp. 1031-1040 ◽  
Author(s):  
R F Ozols ◽  
D C Ihde ◽  
W M Linehan ◽  
J Jacob ◽  
Y Ostchega ◽  
...  
Keyword(s):  
Germ Cell ◽  
Dose Regimen ◽  
Standard Therapy ◽  
Poor Prognosis ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
High Dose Regimen ◽  
Disease Free

We performed a prospective randomized trial of a high-dose chemotherapy regimen v standard cisplatin-based chemotherapy in poor prognosis nonseminomatous germ-cell cancer patients. The high-dose regimen consisting of twice the standard dose of cisplatin (P), along with vinblastine (Ve), bleomycin (B), and the epipodophylotoxin etoposide (VP-16) (V) (PVeBV) was compared to the classic regimen with normal dose cisplatin, vinblastine, and bleomycin (PVeB). Eligibility criteria included large abdominal masses, liver metastases, multiple pulmonary metastases, brain metastases, marked elevations in serum tumor markers (alpha-fetoprotein greater than 1,000 ng/mL or the beta-subunit of human chorionic gonadotropin greater than 10,000 mIU), unfavorable histology (pure choriocarcinoma), or extragonadal germ-cell tumors. Fifty-two consecutive patients with poor prognostic features were randomized to receive either PVeBV or PVeB. The median follow-up is 4 years. Treatment with the high-dose regimen increased the complete remission rate (88% v 67%, P = .14) and was associated with a lower relapse rate (17% v 41%, P = .2). The median survival of patients receiving standard therapy was 30 months, while the median survival for patients receiving the high-dose regimen has not been reached. Actuarial 5-year survival for patients treated with the high-dose regimen is 78%, compared with 48% for patients receiving standard therapy (two-sided Mantel-Cox test = .06). Disease-free survival was also superior for patients randomized to PVeBV (P = .03). Sixty-eight percent of patients (23 of 34) randomized to PVeBV are alive and continuously disease-free, compared with 33% (six of 18) for PVeB (P = .02). The major difference in toxicity between the high-dose regimen and standard therapy was the severity of myelosuppression and the incidence of severe hearing loss. Ninety-one percent of patients treated with PVeBV had a WBC count less than 1,000/microL, compared with 50% of patients receiving PVeB (P less than .05). Hearing aids were recommended for 12 patients who received PVeBV and two who received PVeB. The increased effectiveness of the PVeBV regimen in poor prognosis germ-cell cancer patients may relate to the double-dose cisplatin, the addition of VP-16, or to a synergistic effect of these two drugs.

Clinicopathologic study of uterine endometrial carcinoma in young women aged 40 years and younger

2005 ◽  
Vol 15 (4) ◽  
pp. 657-662 ◽  
Author(s):  
T. Ota ◽  
M. Yoshida ◽  
M. Kimura ◽  
K. Kinoshita
Keyword(s):  
Progesterone Receptor ◽  
Endometrial Carcinoma ◽  
Young Women ◽  
Myometrial Invasion ◽  
Hormonal Treatment ◽  
Primary Treatment ◽  
Careful Consideration ◽  
Clinicopathologic Study ◽  
Well Differentiated ◽  
Adequate Management

To clarify what constitutes the adequate management of uterine endometrial carcinoma in young women, we reviewed clinicopathologically 31 patients aged 40 years and younger between January 1991 and June 2004. As a primary treatment, 12 cases chose hormonal treatment with medroxyprogesterone acetate (MPA; 600 mg/day) due to no findings of myometrial invasion and diagnosis of a grade 1, well-differentiated adenocarcinoma. In remaining 19 cases, surgery was performed. All the 19 patients who received surgery as a primary treatment are alive, with no evidence of a recurrence of the disease. In the 12 patients who received hormonal treatment, 8 patients eventually received a hysterectomy because of recurrence or no response to MPA. Of these eight patients, myometrial invasion was recognized in three patients. One of the eight patients died of the metastasized disease to the liver and brain after hysterectomy. After hormonal treatment, 4 of the 12 patients were exempted from surgery and showed no evidence of recurrence. Two patients had viable children. Progesterone receptor was negative in one case that died. Careful consideration should be given to hormonal treatment with MPA for the conservative management of endometrial carcinoma in young women. Moreover, MPA is not always a consistent management for every patient

Adjuvant chemotherapy for patients with high-grade soft-tissue sarcomas of the extremity.

1988 ◽  
Vol 6 (9) ◽  
pp. 1491-1500 ◽  
Author(s):  
A E Chang ◽  
T Kinsella ◽  
E Glatstein ◽  
A R Baker ◽  
W F Sindelar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Dose Regimen ◽  
Soft Tissue Sarcomas ◽  
Disease Free Survival ◽  
High Dose ◽  
Free Survival ◽  
High Dose Regimen ◽  
Disease Free

We have previously reported the results of a randomized trial that demonstrated the survival benefit of adjuvant chemotherapy in the treatment of patients with high-grade extremity sarcomas compared with no chemotherapy. This regimen included doxorubicin, cyclophosphamide, and methotrexate. This report updates and extends our experience. The median follow-up of this trial is now 7.1 years and reveals a 5-year disease-free survival of 75% and 54% for chemotherapy and no chemotherapy groups, respectively (two-sided P [P2] = .037). The 5-year overall survival for patients in this trial was 83% and 60% for the chemotherapy and no chemotherapy groups, respectively, with a trend towards improved survival in the chemotherapy arm (P2 = .124). Because of doxorubicin-induced cardiomyopathy we performed a subsequent randomized trial comparing this high-dose regimen to reduced cumulative doses of doxorubicin and cyclophosphamide without methotrexate. Eighty-eight patients were entered into this trial which has a median follow-up of 4.4 years. The 5-year disease-free and overall survival for patients treated with the reduced doses of chemotherapy was 72% and 75%, respectively, and was not significantly different from the high-dose regimen. No patients developed congestive heart failure on this study. We conclude that adjuvant chemotherapy improves disease-free survival in patients with extremity soft-tissue sarcomas. The overall survival advantage in patients receiving adjuvant chemotherapy in our initial randomized high-dose chemotherapy trial has diminished though it continues to favor the chemotherapy group. A reduced-dose chemotherapy regimen was found to be comparable to the high-dose regimen.

P5330Evaluating lipid-lowering and anti-atherogenic effect of injectable curcumin in a rabbit model of atherosclerosis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A A Momtazi-Borojeni ◽  
M Banach ◽  
M Majeed ◽  
A Sahebkar
Keyword(s):  
Low Dose ◽  
White Male ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Control Group ◽  
High Dose ◽  
Base Line

Abstract Background and purpose The present study was aimed to evaluate lipid-lowering and anti-atherogenic effect of an intravenous (IV) curcumin in the rabbit fed high cholesterol diet (HCD). Methods New Zealand white male rabbits (4–6 months old, n=25, weight 2.286±0.256 kg)were fed on a normal chow enriched with 0.5% (w/w) cholesterol for 5 weeks. Atherosclerotic rabbits were randomly divided into three group, including a control group receiving intravenous (IV) injection of saline buffer, two treatment groups receiving IV injection of curcumin at two different dosages, 1and 10 mg/kg/week, for 4 weeks. Blood samples were collected from fasted rabbits at pre- (week 5) and post-treatment (week 11) points for analysis of serum lipid levels, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglyceride (TG), and total cholesterol (TC). Aortic arch atherosclerotic lesions were assessed using hematoxylin and eosin (H&E) staining. Results To evaluate curcumin's effects on the hyperlipidemic states and atherosclerosis plaque, HCD-fed rabbits were weekly treated with the injectable curcumin at the low (1mg/kg/week) and high (10 mg/kg/week) doses by 4 weeks. At week 4 in compared with the control group, low-dose curcumin could reduce serum levels of LDL-c, HDL-c, TG, and TC by −6.22% ±1.77, −35.24% ±12.49, −29.84% ±10.14, −14.19% ±5.19, respectively. In the case of high-dose curcumin, serum levels of LDL-c, HDL-c, TG, and TC were changed by −44.36%±3.24, 14.05% ±6.39, −25.92% ±5.57, −56.59% ±10.22, respectively, when compared with the control group at week 4. Low-dose curcumin after 4 weeks' treatment could reduce serum levels LDL-c, HDL-c, TG, and TC up to 103±28 mg/dL, 18.33±4.66 mg/dL, 97.5±31 mg/dL, and 356.5±19.5 mg/dL, respectively, when compared with the base line levels (week 0). High-dose curcumin after 4 weeks' treatment could decrease serum levels of LDL-c, HDL-c, TG, HDL-c, and TC up to 207±17.04 mg/dL, 15.5±0.5 mg/dL, 333±40 mg/dL, and 514.5±22.23 mg/dL, respectively (Figure). H&E staining declared that atherosclerotic lesion grades were significantly lower in the curcumin-treated groups than the control group. Changes of lipids in rabbits on curcumin Conclusions The injectable curcumin at the low (1mg/kg) and high (10 mg/kg) could significantly improve dyslipidemia and alleviate atherosclerotic lesion in HCD-induced atherosclerotic rabbits.

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