scholarly journals Prospective Parallel Randomized, Double-Blind, Double-Dummy Controlled Clinical Trial Comparing Clomiphene Citrate and Metformin as the First-Line Treatment for Ovulation Induction in Nonobese Anovulatory Women with Polycystic Ovary Syndrome

2005 ◽  
Vol 90 (7) ◽  
pp. 4068-4074 ◽  
Author(s):  
Stefano Palomba ◽  
Francesco Orio ◽  
Angela Falbo ◽  
Francesco Manguso ◽  
Tiziana Russo ◽  
...  
Keyword(s):  
Polycystic Ovary ◽  
Clomiphene Citrate ◽  
Controlled Clinical Trial ◽  
Line Treatment ◽  
First Line ◽  
Ovary Syndrome ◽  
Double Blind ◽  
Group A ◽  
Group B ◽  
First Line Treatment

Abstract Context: Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients. Objective: The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS. Design: We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial. Setting: The study was conducted at the University “Magna Graecia” of Catanzaro, Catanzaro, Italy. Patients: One hundred nonobese primary infertile anovulatory women with PCOS participated. Interventions: We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each. Mean outcome measures: The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates. Results: The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P < 0.001). Conclusions: Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women.

Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4000-4000 ◽  
Author(s):  
E. Van Cutsem ◽  
M. Nowacki ◽  
I. Lang ◽  
S. Cascinu ◽  
I. Shchepotin ◽  
...  
Keyword(s):  
Response Rate ◽  
Performance Status ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Ecog Performance Status ◽  
Skin Reactions ◽  
Group A ◽  
Group B ◽  
First Line Treatment

4000 Background: Cetuximab in combination with irinotecan-based regimens has proven activity in previously-treated patients (pts) with mCRC. The present trial investigated the effectiveness of cetuximab in combination with standard FOLFIRI compared with FOLFIRI alone in the first-line treatment of pts with epidermal growth factor receptor (EGFR)-expressing mCRC. Methods: Pts were randomized 1:1 to receive either cetuximab (400 mg/m2 initial dose then 250 mg/m2/week [w]) plus FOLFIRI q 2 w (irinotecan 180 mg/m2, FA 400 mg/m2, 5-FU bolus 400 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 hours) (Group A) or FOLFIRI alone (Group B). The primary endpoint was progression-free survival (PFS), with secondary endpoints of overall survival (OS), response rate (RR), disease control rate and safety. 633 events were required to statistically differentiate PFS between groups with 80% power. Results: Between August 2004 and October 2005, 1,217 pts were randomized, 608 to Group A and 609 to Group B (60% male, median age 61 [19–84], ECOG performance status: 0=54%; 1=43.5%; 2=3.5%). Median PFS was significantly longer for Group A compared to Group B (8,9 months [8 - 9,5] for Group A vs. 8 months [7.6 - 9] for Group B, p=0.036). Response Rate was also significantly increased by cetuximab (46.9% vs. 38.7%, p=0.005). Treatment was generally well tolerated with neutropenia (26.7% Group A, 23.3% Group B), diarrhea (15.2% and 10.5% respectively) and skin reactions (18.7% and 0.2% respectively) being the most common grade 3/4 adverse events. Conclusions: Cetuximab in combination with FOLFIRI significantly increases response rate and significantly prolongs PFS in the first-line treatment of pts with mCRC, reducing the relative risk of progression by approximately 15%. Treatment-related side effects of cetuximab in combination with FOLFIRI were as expected, with diarrhea being moderately and skin reactions significantly more frequent as compared to FOLFIRI alone. [Table: see text]

scholarly journals COMPARISON OF EFFECT OF CLOMIPHENE CITRATE WITH ESTRADIOL VALERATE V/S LETROZOLE ON PREGNANCY RATE IN INFERTILE WOMEN WITH PCOS

2020 ◽  
Vol 4 (7) ◽  
Author(s):  
Mendiratta Suman ◽  
Joshi Amit Kumar ◽  
Netra Harendra Kumar
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Pregnancy Rate ◽  
Polycystic Ovary ◽  
Endometrial Thickness ◽  
Clomiphene Citrate ◽  
Estradiol Valerate ◽  
Ovary Syndrome ◽  
Infertile Women ◽  
Group A ◽  
Group B

Background: Polycystic ovary syndrome is the commonest endocrinopathy in anovulatory infertility in young women. It is estimated that infertility affects 10 to 14% of the Indian population of which approximately 25-30% part occupied by PCOS. Methods: This prospective study enrolled 180 infertile women with PCOS, age 21-35 yrs who have taken 1 cycle of clomiphene citrate 100 mg, endometrial thickness <7 mm inspite of follicles greater than 18 mm. Half of them treated with clomiphene citrate with estradiol valerate and remaining half with letrozole. Results: In Group-A treated with clomiphene citrate with estradiol valerate 13 patients (16.3%) conceived and in Group-B treated with letrozole 26 patients (32.5%) conceived. Conclusion: Pregnancy rate is higher in group which treatment with letrozole in comparison with clomiphene citrate plus estradiol valerate. Keywords: Polycystic ovary syndrome, Infertility, Pregnancy rate

Comparison of Clomiphene Citrate Plus N-Acetyl Cysteine and Clomiphene Citrate Alone for Induction of Ovulation in Polycystic Ovary Syndrome

2021 ◽  
Vol 15 (6) ◽  
pp. 1253-1255
Author(s):  
S. Waseem ◽  
S. Gohar ◽  
M. Afzal ◽  
Z. Wali
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovarian Syndrome ◽  
Polycystic Ovary ◽  
Clomiphene Citrate ◽  
Ovary Syndrome ◽  
Obstetrics And Gynaecology ◽  
Group A ◽  
Acetyl Cysteine ◽  
Group B ◽  
Ovarian Syndrome

Aim: To compare the frequency of ovulation with clomiphene citrate plus N-acetyl cysteine versus clomiphene citrate alone in married females presenting with polycystic ovarian syndrome. Study design: Randomized clinical trial Place and duration of study: Department of Obstetrics and Gynaecology, Unit-3 Jinnah Hospital, Lahore from 1st September 2018 to 28th February 2019. Methodology: A total of 60 patients (30 in each group) were enrolled. In group A, females were prescribed clomiphene citrate 50-mg tablets twice daily with N-acetyl cysteine 1200 mg/day orally for 5 days starting on day 3 of the menstrual cycle and in group B, females were prescribed clomiphene citrate 50-mg tablets twice daily. Results: Patients ranged between 18-35 years of age. Mean age of the patients was 28.5±3.3 and 28.1±3.1 years in group A and B, respectively. Mean duration of marriage in group A was 3.4±0.9 and in group B 3.5±0.9 year. Mean BMI in group-A was 3.4±0.9 while in group-B 3.5±0.9 (kg/m2). Ovulation was observed at 1st month in group A was 12 (40%) and in group B 9 (30%). Ovulation was observed at 2nd month in group A was 16 (53.3%) and in group B 13 (43.3%). In 3rd months ovulation was seen in 19 patients (63.3%) of group A and 18 patients (60%) of group B. Stratification for age and BMI was also carried out. Conclusion: This study could not find any clinical superiority for clomiphene citrate plus N-acetyl cysteine versus clomiphene citrate alone in term of ovulation rate. Keywords: N-acetyl cysteine, Polycystic ovary syndrome, Ovulation induction

Five-year survival analysis of interferon-a plus sorafenib versus sorafenib monotherapy as first-line treatment for metastatic clear cell renal cell carcinoma.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 486-486
Author(s):  
Ye Ding-Wei ◽  
Zhang Hai-Lang
Keyword(s):  
Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Line Treatment ◽  
First Line ◽  
Cell Renal Cell Carcinoma ◽  
Group A ◽  
Group B ◽  
First Line Treatment

486 Background: We compared the short- and long-term efficacy and safety of interferon-a plus sorafenib with sorafenib monotherapy as first-line treatment in metastatic clear cell renal cell carcinoma (mRCC) patients. Methods: mRCC patients who had not received systemic treatment were administered either interferon-a (300 MIU IM every other day) plus sorafenib (400 mg bid n=24, Group A) or sorafenib monotherapy (400 mg bid; n=24, Group B). Objective responses (OR; RECIST criterion ver 1.0) and differences in OR, progression-free survival (PFS), overall survival (OS) and toxicity were compared. Results: Sixty eight percent males were present in both the groups with comparable baseline demographic characteristics. After a median follow-up of 68 months, the OR was comparable (p=0.726) in Group A vs B; complete remission (1 vs 0 cases), partial remission (6 vs 7 cases), stable disease (14 vs 15 cases), and progressive disease (3 vs 3 cases). No significant difference was observed in the median PFS (p=0.965) and median OS (p=0.223) between both groups [9.4 months (95% CI: 5.8-17.4), Group A vs 14.0 months (95% CI: 9.9-18.0), Group B] and [32.9 months (95% CI: 8.2-87.1), Group A vs 20.4 months (95% CI: 16.2-24.6), Group B], respectively. The 5-year survival rate was higher in Group A vs B (46% vs 25%). Toxicity symptoms like fever (13 vs 3 cases), fatigue (15 vs 9 cases) and neutropenia (6 vs 1 cases) were more pronounced in Group A vs B. The incidence of hand and foot skin reactions, alopecia, rash, hypertension, liver dysfunction, hypophosphatemia, anemia, and other toxicities was similar in both groups. There were 14 (58.3%) and 8 (33.3%) cases of dosage reduction or suspension in Groups A and B, respectively. Conclusions: Short-term effect of interferon-a plus sorafenib as first-line treatment for mRCC was comparable to sorafenib monotherapy in terms of OR and PFS. Although higher toxicity was reported for interferon-a plus sorafenib, the combination holds promise for improving long-term OS.

scholarly journals Very Poor Outcome of Patients with Relapsed/Refractory Aggressive B Cell Lymphoma after Autologous Stem Cell Transplantation (ASCT) or High Dose of Methotrexate and Cytarabine (HD-MTX/ARA-C) Regimens in the Clinical Care Setting

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4232-4232
Author(s):  
Nicola Bianchetti ◽  
Alessandra Tucci ◽  
Alessandro Re ◽  
Chiara Pagani ◽  
Chiara Cattaneo ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Board ◽  
Line Treatment ◽  
First Line ◽  
Curative Intent ◽  
Group A ◽  
Group B ◽  
First Line Treatment

Abstract INTRODUCTION: Although diffuse large B cell lymphoma (DLBCL) is considered a curable disease in the immunochemotherapy (ICT) era, about 40% of patients relapse or are refractory to first line treatment, representing an unmet clinical need. The role of upfront autotransplantation (ASCT) in high-risk cases is still debated, while its role in relapsed/refractory (R/R) disease is established in all guidelines. However less than 50% are actually cured with salvage ASCT (Gisselbrecht C et al, J Clin Oncol. 2010) and outcome of patients who relapse after ASCT is very poor (Crump M. et al, Blood 2017; Van Den Neste E et al, BMT 2017). Prognosis of aggressive lymphomas with characteristics intermediate with Burkitt's lymphoma (BCLU), recently reclassified (WHO 2016) as high grade lymphoma, unspecified with or without c-myc translocation, is less favourable. Regimens containing HD-MTX/ARA-C were generally used to treat these lymphoma subtypes as well as lymphoma with central nervous system (CNS) localization. Aim of this study was to evaluate the prevalence and outcome of R/R lymphoma after upfront or salvage ASCT or after HD-MTX/ARA-C regimens in the clinical care setting and to identify potential salvage approaches. PATIENTS and METHODS: We retrospectively analysed all consecutive HIV-negative patients seen at our Institute from January 2008 to December 2016 with de novo or transformed DLBCL, Primary mediastinal B-cell lymphoma or high-grade lymphoma/BCLU. First-line treatment used was R-CHOP/CHOP-like regimens. Consolidation with ASCT was performed in all high/intermediate-high IPI risk patients less than 65 years old, while salvage ASCT was performed after salvage ICT for R/R disease; HD-MTX/ARA-C regimens were used in DLBCL patients with CNS involvement or in BCLU cases. Relapsed or refractory patients after upfront or salvage ASCT or after HD-MTX/ARA-C were selected and their demographic and histological features as well as their outcome was analysed in term of duration of Response (DOR) from ASCT or MTX/ARA-C regimen to relapse and Overall Survival (OS) from relapse to the last follow-up or death. We recorded salvage treatments carried out according to age, performance status, available clinical protocols or international guidelines (more than one line in some patients). RESULTS: Among 571 patients consecutively seen during the time period, 156 (27.3%) proved refractory or relapsed after first-line treatment. ASCT was performed in 86 patients as consolidation (group A) and in 33 as salvage (group B). First line HD-MTX/ARA-C regimens were used in 16 patients (group C). Relapse occurred in 9/86 group A (10%), 20/33 group B (61%) and 8/16 group C (50%) patients respectively, representing 6.5% of the whole patients initially diagnosed. First relapse occurred after a median DOR of 4, 7, and 3.5 months in group A, B and C respectively. The main demographic and histological characteristics of relapsed patients are summarized in the Table 1, which also shows treatments used after relapse. Response rates in patients treated with curative intent were 29% (6/21). Mortality rates were high in all groups (78%, 90% and 100% respectively), with an OS significantly better in group A comparing to group B and C patients (p 0.0243) (Fig.1a) and in patients treated with curative intent compared to patients that received palliation (p &lt;0.0001) (Fig.1b). Four patients only are currently alive, 2 in group A at 84 and 3 months after allotransplantation and 2 in group B at 15 months after HD-MTX/ARA-C for CNS recurrence and after R-DHAP ICT with lenalidomide maintenance still ongoing at month 36th as part of a study protocol. The cause of death for all patients was progression of disease. CONCLUSIONS: This analysis shows the very poor prognosis of patients with aggressive lymphoma relapsing after high dose therapy (ASCT or MTX/ARA-C). The recurrence of disease in these patients is early and salvage therapies are ineffective in most of the cases, although trying to treat these patients with curative intent shows a survival advantage over palliation. Patients treated with multiple lines of chemotherapy (group B) or with upfront HD-MTX/ARA-C (group C) have the worse prognosis. These data justify intensive follow-up programs during the first year after the end of therapy, and underline the need to develop new therapeutic strategies for this setting of patients, which could represent an ideal indication for CAR-T cell treatments. Disclosures Rossi: GILEAD: Other: ADVISORY BOARD; SANOFI: Other: ADVISORY BOARD; NOVARTIS: Honoraria; ABBVIE: Other: ADVISORY BOARD; CELGENE: Other: ADVISORY BOARD; AMGEN: Other: ADVISORY BOARD; JAZZ: Other: ADVISORY BOARD; JANNSEN: Other; MUNDIPHARMA: Honoraria; BMS: Honoraria; PFIZER: Other: ADVISORY BOARD; TEVA: Other: ADVISORY BOARD; ROCHE: Other: Advisory Board; SANDOZ: Honoraria.

scholarly journals Impact of Age on Efficacy, Safety, and Long-Term Outcome of Chronic Myeloid Leukemia (CML) Patients Treated in First-Line with Nilotinib: An Analysis of the Gimema CML Working Party

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3068-3068 ◽  
Author(s):  
Gabriele Gugliotta ◽  
Fausto Castagnetti ◽  
Massimo Breccia ◽  
Mariella D'Adda ◽  
Fabio Stagno ◽  
...  
Keyword(s):  
Research Funding ◽  
Age Groups ◽  
Molecular Response ◽  
Line Treatment ◽  
First Line ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Group A ◽  
Group B ◽  
First Line Treatment

Abstract Background: In chronic phase (CP) chronic myeloid leukemia (CML) the disease characteristics at diagnosis, risk distribution, probability of transformation to accelerated/blast phase (AP/BP), and toxicities may vary according to age. Nilotinib has shown better efficacy compared to imatinib, but it has been associated to a higher incidence of arterial thrombotic events (ATEs). Little is known on the efficacy, safety and long-term outcome of nilotinib treated patients in different age groups. Aims: To investigate the efficacy and safety, particularly the cardiovascular safety, of first-line treatment with nilotinib according to age distribution. Methods: We analyzed 345 patients ≥ 18 years of age with CP CML enrolled in clinical trials of the GIMEMA CML WP investigating nilotinib as first-line treatment. Patients were treated with: nilotinib 400 mg BID (n=73); rotation of nilotinib 400 mg BID / imatinib 400 mg OD (3-month periods for each drug)(n=123); nilotinib 300 mg BID (n=149). The median follow-up was 58 months. We divided the patients in 3 groups of age (table): 18-49 years (group A, 147 pts, median age: 39 years); 50-64 years (group B, 109 pts, median age 58 years); and ≥ 65 years (group C, 89 pts, median age 71 years). We analyzed in detail the response rates, events and outcome. Definitions: Major molecular response (MMR): BCR-ABL≤0.1% (IS), with > 10.000 ABL copies; MR4: BCR-ABL≤0.01% (IS), with > 10.000 ABL copies. Events: permanent discontinuation of nilotinib for any reason, including adverse events, progression to AP/BP, or deaths. ATEs: peripheral arterial obstructive disease (PAOD), acute coronary syndrome, chronic ischemic heart disease, significant carotid stenosis and ischemic stroke, or other significant ischemic events. Results: EUTOS high risk patients were: 8.8, 5.5, 1.1% in group A, B, and C, respectively (p=0.048). We did not observe significant differences in molecular response rates (table), including BCR-ABL/ABL <10% at 3 months, MMR and MR4 at 12 months, and cumulative incidences by 5 years of MR3 and MR4. Events leading to permanent nilotinib discontinuations occurred in 31%, 29%, and 42% of group A, B, and C, respectively (p=0.049). Overall, 29 ATEs were recorded, with higher rates, as expected, in elderly patients (group A: 2%; B: 11%; C: 15.7%; p=0.006); relative risk for ATEs in group B vs. A: 5; relative risk in group C vs. A: 6.7. ATEs were the reason for permanent nilotinib discontinuation in 2% of pts 18-49 years, 7.3% of pts 50-64 years, and 11.2% of pts > 65 years (p=0.015). Progressions to AP/BP were significantly more frequent in younger (18 - 49 years) patients (6.8%) compared to older (> 50 years) patients (1.5%), p= 0.019. Overall, 19 patients died (group A: 4.8%; B: 2.8%; C: 10%). In patients < 65 years all deaths (10) were leukemia-related, while in patients >65 years, all but one (8/9) deaths were leukemia-unrelated. The 6-year overall-survival was 94%, 97%, and 84% in pts 18-49 years, 50-64 years, and > 65 years of age (p=0.12) Summary/Conclusion: Nilotinib as first-line treatment of newly diagnosed CP CML patients showed high rates of molecular responses in all age groups. However, compared to older patients, significant more progressions occurred in younger (18-49 years) ones; the causes of death in this group were all leukemia-related. In contrast, in elderly patients (>65 years) the causes of death were almost all leukemia-unrelated. ATEs were rare (2%) in patients of 18-49 years, while high rates (> 10%) of ATEs were recorded in those of 50-64 years; as expected, ATEs occurred even more frequently in patients > 65 years. These data suggest that while in patients > 50 years more attention should be focused on the prevention of ATEs, in younger ones more efforts are needed to avoid the progression of CML to accelerated/blast phase. Disclosures Gugliotta: Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Castagnetti:Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; ARIAD Pharmaceuticals: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Breccia:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Ariad: Honoraria; Pfizer: Honoraria. Carella:Millenium: Speakers Bureau; Genentech: Speakers Bureau. Tiribelli:Ariad Pharmaceuticals: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Soverini:Ariad: Consultancy; Bristol-Myers Squibb: Consultancy; Novartis: Consultancy. Cavo:Janssen-Cilag: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Millennium: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Martinelli:Pfizer: Consultancy, Speakers Bureau; ARIAD: Consultancy; Roche: Consultancy; MSD: Consultancy; Novartis: Speakers Bureau; Amgen: Consultancy; Genentech: Consultancy; BMS: Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; ARIAD: Consultancy; Roche: Consultancy; MSD: Consultancy; Amgen: Consultancy; Genentech: Consultancy. Saglio:Ariad: Consultancy; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy. Baccarani:Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Other: personal fees, Speakers Bureau; Ariad: Honoraria, Other: personal fees, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Rosti:Roche: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Incyte: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.

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