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41.
Laurien J. Zeverijn Eleonora J. Looze Subotheni Thavaneswaran J. Maxime van Berge Henegouwen Robert J. Simes Louisa R. Hoes Katrin M. Sjoquist Hanneke van der Wijngaart Lucille Sebastian Birgit S. Geurts Chee K. Lee Gijsbrecht F. de Wit David Espinoza Paul Roepman Frank P. Lin Anne M. L. Jansen Wendy W. J. de Leng Vincent van der Noort Lindsay V. M. Leek Filip Y. F. L. de Vos Carla M. L. van Herpen Hans Gelderblom Henk M. W. Verheul David M. Thomas Emile E. Voest 《International journal of cancer. Journal international du cancer》2023,153(7):1413-1422
The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible. 相似文献
42.
Norio Itokawa Masanori Atsukawa Akihito Tsubota Noritomo Shimada Hidenori Toyoda Koichi Takaguchi Atsushi Hiraoka Tomonori Senoh Mai Koeda Yuji Yoshida Tomomi Okubo Taeang Arai Korenobu Hayama Ai Nakagawa-Iwashita Chisa Kondo Katsuhiko Iwakiri 《Internal medicine (Tokyo, Japan)》2021,60(4):507
Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10-2 and 4.42×10-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B. 相似文献
43.
Ping Zhang Liangliang Ma Xiaojie Wang Ruijie Zhang Yuting Dong 《The Journal of international medical research》2020,48(12)
Ovarian cancer remains the most lethal gynecological malignant tumor, with relapse occurring in approximately 70% of advanced cases. Anlotinib is an oral small-molecule multi-targeted tyrosine kinase inhibitor that can resist neoangiogenesis and inhibit tumor growth. Previous research demonstrated clinical antitumor activity of anlotinib in various cancers. We report the case of an elderly woman with advanced ovarian cancer who received anlotinib after failure of multiple-line chemotherapy. A partial response was observed after six cycles of anlotinib monotherapy, with a reduction in the size of the metastases and significantly decreased serum CA125 levels from 1832.7 U/mL to 118.7 U/mL. She continued to take anlotinib, with a progression-free survival time of more than 4 months. Only mild hypertension was observed during the treatment. Anlotinib monotherapy may be a novel therapeutic option for patients with advanced ovarian cancer. 相似文献
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Long‐term efficacy and safety of ertugliflozin monotherapy in patients with inadequately controlled T2DM despite diet and exercise: VERTIS MONO extension study 下载免费PDF全文
47.
《Best Practice & Research: Clinical Haematology》2018,31(1):65-72
BackgroundSMZL is a relatively rare low grade B-cell lymphoma, characterized usually by an indolent clinical behavior. Since there is no prospective randomized trials to establish the best treatment approach, decision on therapeutic management should be based on the available retrospective series. Based on these data, rituximab and splenectomy appear to be the most effective. Splenectomy represented the standard treatment modality until early 2000s. More than 90% of the patients present quick amelioration of splenomegaly related symptoms along with improvement of cytopenias related to hypersplenism. The median progression free survival was 8.25 years in the largest series of patients published so far, while the median 5- and 10- year OS were 84% and 67%, respectively. Responses to splenectomy are not complete since extrasplenic disease persists. Patients with heavy bone marrow infiltration, lymphadenopathy or other disease localization besides the spleen are not good candidates for splenectomy. Furthermore splenectomy is a major surgical procedure accompanied by acute perioperative complications as well as late toxicities mainly due to infections. For that reasons splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk. On the other hand rituximab monotherapy displays high efficacy with minimal toxicity. Several published series have shown an ORR more than 90%, with high CR rates (∼50%). The 10-year PFS and OS were 63% and 85%, respectively in a series of 104 SMZL patients. The role of rituximab maintenance has been investigated by only one group. Based on these data, maintenance with rituximab further improved the quality of responses by increasing significantly the CR rates (from 42% at the end of induction to 71% at the end of maintenance treatment), as well as the duration of responses: 7-year PFS was 75% for those patients who received maintenance vs 39% for those who did not (p < 0.0004). However no difference in OS has been noticed between the two groups, so far. Summarizing the above data, it is obvious that Rituximab monotherapy is associated with high response rates, long response duration and favorable safety profile, rendering it as the treatment of choice in SMZL. 相似文献
48.
Elia Rosi Leonardo Pescitelli Federica Ricceri Antonella Di Cesare Andrea Novelli Nicola Pimpinelli Francesca Prignano 《Dermatologic therapy》2019,32(2)
The rifampicin (RF)–clindamycin (CL) combination is recommended as first line therapy in moderate to severe Hidradenitis Suppurativa (HS) by European S1 guidelines. Although prolonged use of RF should be discouraged, there are currently few alternatives to this combination therapy. The aim of the present study was to assess retrospectively the efficacy of oral CL monotherapy in patients diagnosed with HS. In the period January 2017–May 2018, 31 HS patients who received a 300 mg b.i.d. oral dose of CL were studied retrospectively. Efficacy of the treatment was evaluated by comparing the main HS severity scores (Sartorius score modified by Revuz, Hidradenitis Suppurativa Physician Global Assessment [HS‐PGA] and International Hidradenitis Suppurativa Severity Score System [IHS4]) before (W0) and after (W12) CL oral therapy. CL efficacy was demonstrated by the extreme and significant reduction of all three disease severity parameters during the 12‐week period (p ≤ .01). There was also a statistically significant change in the mean visual analogue scale for pain. The present study demonstrates the efficacy of oral CL monotherapy as RF‐sparing regimen alternative to RF–CL combination in a selected group of patients. 相似文献
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孙伟 《中国实用妇科与产科杂志》2015,31(1):41-44
该文从中药辨证施治、中药周期疗法、单方单药治疗、针灸治疗、中药外敷治疗等方面综述了近年中药促排卵在临床和实验的研究概况,说明了中医药促排卵具有良好的临床作用和发展前景,同时存在一些问题,建议从中西医结合角度研究以探索更好的促排卵方法,提高临床的疗效。 相似文献