Safety and efficacy of thalidomide in recurrent epithelial ovarian and peritoneal carcinoma

Chan, John K.; Manuel, Michael; Ciaravino, Giuseppe; Cheung, Michael K.; Husain, Amreen; Teng, Nelson N.H.

doi:10.1016/j.ygyno.2006.05.035

Cited by 16 publications

(9 citation statements)

References 26 publications

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“…All three responders had peritoneal disease. Another phase I clinical trial also used thalidomide in 17 heavily pretreated patients with recurrent ovarian and primary peritoneal cancers [18]. The initial dose was 100 mg/day with dose escalations up to 1,200 mg/day as tolerated.…”

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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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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“…So far, there are only a few clinical studies on the efficacy of thalidomide in patients with EOC. Thalidomide was given orally (100-400 mg/day) to heavily pretreated patients with advanced or recurrent EOC either as a single agent [39][40][41][42] or in combination with systemic chemotherapy [43]. Thalidomide was well tolerated and had modest activity in heavily pretreated patients with advanced or recurrent EOC.…”

Section: Discussionmentioning

confidence: 99%

Thalidomide distinctly affected TNF-α, IL-6 and MMP secretion by an ovarian cancer cell line (SKOV-3) and primary ovarian cancer cells

Piura¹,

Medina²,

Rabinovich³

et al. 2013

European Cytokine Network

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Background. Thalidomide inhibits TNF-␣ production in lipopolysaccharide-stimulated monocytes. The aim of this study was to evaluate the effect of thalidomide on TNF-␣, IL-6 and MMP secretion in epithelial ovarian carcinoma cells. Materials and methods. SKOV-3 cells and primary epithelial ovarian carcinoma cells were cultured in the presence of various concentrations of thalidomide. Cell proliferation was examined by MTT proliferation assay. TNF-␣ and IL-6 levels were determined in the supernatants of the cell cultures by ELISA, and MMP activity was examined by gelatin zymography. Results. Thalidomide did not significantly affect the proliferation and growth of SKOV-3 cells. However, it decreased significantly the capacity of SKOV-3 cells and primary epithelial ovarian carcinoma cells to secrete TNF-␣. Thalidomide also significantly decreased the capacity of SKOV-3 cells, but not primary epithelial ovarian carcinoma cells, to secrete MMP-9 and MMP-2. However, thalidomide did not affect IL-6 secretion in SKOV-3 cells or primary epithelial ovarian carcinoma cells. Conclusion. Our study suggests that thalidomide distinctly affected TNF-␣, IL-6 and MMPs secretion by an ovarian carcinoma cell line (SKOV-3) and primary ovarian cancer cells. This might suggest a different susceptibility of these two types of cells to thalidomide, and/or that the mechanisms of secretion of the factors examined are differently regulated in these cells. Our results may deepen our understanding the mechanism/s of action of thalidomide in ovarian carcinoma cells. The results might have important implications in future therapeutic strategies that will incorporate thalidomide and other cytokine inhibitors in the treatment of epithelial ovarian carcinoma.

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“…Three papers reviewed the indications, mechanisms and side effects of thalidomide in specific disease and interstitial pneumonitis was not quoted in any of these studies as an adverse effect of the drug [11][12][13]. Five studies reported cases of likely drug-induced interstitial pneumonitis while on thalidomide alone as treatment for multiple myeloma [3][4][5][6][7].…”

Section: Figurementioning

confidence: 99%

A rare pulmonary complication of myeloma therapy

Schrieber¹,

Xu-Holland²,

Walker³

et al. 2014

Breathe

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Safety and efficacy of thalidomide in recurrent epithelial ovarian and peritoneal carcinoma

Cited by 16 publications

References 26 publications

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

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

Thalidomide distinctly affected TNF-α, IL-6 and MMP secretion by an ovarian cancer cell line (SKOV-3) and primary ovarian cancer cells

A rare pulmonary complication of myeloma therapy

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