Ovarian and Papillary-Serous Peritoneal Carcinoma: Pilot Study With Thalidomide

Abramson, Neil; Stokes, P. K.; Mathew, Luke; Marks, Alan R.; Harris, Jeffrey M.

doi:10.1200/jco.2002.20.4.1147

Cited by 30 publications

(12 citation statements)

References 2 publications

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“…It has become particularly important in the treatment of advanced multiple myeloma and is now considered standard in the management of this disease [11]. Thalidomide has been investigated in the treatment of gynecologic malignancies including recurrent ovarian and primary peritoneal cancer, and a 37% response rate was reported in one small phase II trial in patients with chemo-refractory 37 % [12].…”

Section: Introductionmentioning

confidence: 99%

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

McMeekin

Sill

Benbrook

et al. 2007

Gynecologic Oncology

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Objectives-A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of thalidomide in persistent or recurrent endometrial cancer refractory to cytotoxic chemotherapy, and to correlate angiogenesis biomarker expression with clinical outcome.Methods-Consenting patients were treated until progression or intolerable toxicity with an oral starting dose of 200 mg thalidomide/day that was to increase by 200 mg every 2 weeks to a target dose of 1000 mg/day. Vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), and soluble endothelial protein C receptor (sEPCR) were analyzed by ELISA in pre and post-treatment specimens.Results-Twenty-four of 27 patients enrolled in the study were eligible, of whom 2 reached the target dose, 8 progressed before achieving the target dose and 14 refused or had toxicity that prohibited escalation. Two patients (8.3%) remained progression-free ≥ 6 months. There were 3 (12.5%) with partial responses, 2 (8.3%) with stable disease, 15 (62.5%) with increasing disease, and 4 (16.7%) who were inevaluable for response. Median progression-free survival and overall survival Précis: Thalidomide has minimal activity in chemo-refractory endometrial cancer as judged by the ability to prolong progression-free survival greater than 6 months.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Introductionmentioning

confidence: 99%

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

McMeekin

Sill

Benbrook

et al. 2007

Gynecologic Oncology

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“…The use of thalidomide for peritoneal disease was described in a pilot study of ten patients (seven with ovarian adenocarcinoma, two with papillary serous peritoneal adenocarcinoma of the peritoneum, and one had both) [17]. All patients had failed standard chemotherapy regimens.…”

Section: Discussionmentioning

confidence: 99%

Phase II Trial of Adjuvant Oral Thalidomide Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Disease from Colorectal/Appendiceal Cancer

Shen

Thomas²,

Fenstermaker

et al. 2014

J Gastrointest Canc

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Purpose This phase II single-institution trial of adjuvant thalidomide after cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with appendiceal and colorectal malignancies sought to detect an improvement in progression-free survival (PFS) from 7 to 12 months. Methods Eligible patients received CS, HIPEC, and baseline imaging, followed by pretreatment thalidomide counseling. All participants were then started on a 28-day regimen of thalidomide, 100 mg by mouth at bedtime, followed by 200 mg for 4 weeks, followed by 300 mg as the final maintenance dose, as tolerated. Results Twenty-seven eligible patients (median age 52 years; 52%appendiceal/48%colorectal) were enrolled on this trial and included in the analysis, and 26 were evaluable for response. Eighteen patients demonstrated stable disease on adjuvant thalidomide, while eight showed evidence of progression. Approximately 30 % of the patients withdrew due to toxicity. Grade 3/4 toxicities included neurological disorders (16 %), nausea (12 %), vomiting (8 %), and thromboembolism (8 %). Median overall survival (OS) and PFS were 43.0 and 9.3months, respectively, and median follow-up was 40.4 months. Multivariate modeling showed significant improvements in PFS and OS for appendiceal patients and those with R0 or R1 resections. On an intent-to-treat analysis, the PFS of the study group was 9 months. Conclusions Based on these findings, thalidomide cannot be recommended as adjuvant therapy after CS and HIPEC for gastrointestinal malignancies. Further research is needed to identify active agents in this population.

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“…Abramson et al [192] conducted a pilot study with thalidomide for refractory and resistant ovarian or peritoneal carcinoma. Most patients received 400 mg/day.…”

Section: Potential Therapies Targeting Angiogenesismentioning

confidence: 98%

Targeted Therapies in Gynecologic Cancers

Chon¹,

Hu²,

Kavanagh³

2006

CCDT

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With the rapid development of high-throughput techniques for identifying novel specific molecular targets in human cancer over the past few years, attention to targeted cancer therapy has dramatically increased. The term "targeted cancer therapy" refers to a new generation of drugs designed to interfere with a specific molecular target that is believed to play a critical role in tumor growth or progression, is not expressed significantly in normal cells, and is correlated with clinical outcome. There has been a rapid increase in the identification of targets that have potential therapeutic application. The clinical success of the small-molecule kinase inhibitor imatinib mesylate in chronic myeloid leukemia and gastrointestinal stromal tumors has accelerated the development of a new era of molecular targeted cancer therapy. The number of agents under preclinical and clinical investigation has grown accordingly. This emphasis on molecular biology and genetics has also resulted in significant changes in the treatment of gynecologic cancers. Several promising drugs targeting tyrosine kinases (EGFR and Her-2/Neu), mTOR, Raf kinase, proteasome, and histone deacetylases, as well as drugs affecting apoptosis and mitosis, are under development for clinical application. However, some clinical trials of p53 gene therapies and farnesyl transferase inhibitors have had limited success. In this review, we will focus on potential novel targets in gynecologic cancer and the development of targeted therapy and its clinical applications in gynecologic cancer.

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Ovarian and Papillary-Serous Peritoneal Carcinoma: Pilot Study With Thalidomide

Cited by 30 publications

References 2 publications

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

Phase II Trial of Adjuvant Oral Thalidomide Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Disease from Colorectal/Appendiceal Cancer

Targeted Therapies in Gynecologic Cancers

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