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

McMeekin, D. Scott; Sill, Michael W.; Benbrook, Doris M.; Darcy, Kathleen M.; Stearns-Kurosawa, Deborah J.; Eaton, Lynne; Yamada, S. Diane

doi:10.1016/j.ygyno.2007.01.019

Cited by 87 publications

(59 citation statements)

References 42 publications

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“…Negligible activity was observed in phase II trials testing the following drugs as single agents: cisplatin, mitoxantrone, amonifide, oral etoposide, diazoquone (AZQ), intravenous etoposide, topotecan, paclitaxel, thalidomide, and trimetrexate [3][4][5][6][7][8][9][10][11][12][13][14]. Single agents that show moderate activity in leiomyosarcoma include ifosfamide (response rate 17.2%), doxorubicin (response rate 25%), and gemcitabine (bolus infusion achieved a 20% response rate among women with uterine leiomyosarcoma who had received 0-1 prior cytotoxic regimen) [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Fixed-dose rate gemcitabine plus docetaxel as second-line therapy for metastatic uterine leiomyosarcoma: A Gynecologic Oncology Group phase II study

Hensley

Blessing

Mannel

et al. 2008

Gynecologic Oncology

243

133

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Objective-Doxorubicin-based treatment is standard therapy for metastatic uterine leiomyosarcoma. There is no standard second-line therapy. We determined activity of fixed-dose rate gemcitabine plus docetaxel as second-line treatment for metastatic uterine leiomyosarcoma.Methods-Eligible women with unresectable uterine leiomyosarcoma progressing after prior cytotoxic therapy were treated with gemcitabine 900 mg/m 2 days one and eight over 90 minutes, plus docetaxel 100 mg/m 2 on day 8 of a 21-day cycle with granulocyte growth factor. Patients with prior pelvic radiation received lower doses. Response Evaluation Criteria in Solid Tumors (RECIST) response was assessed by computed tomography (CT).Results-Forty-eight of 51 women were evaluable for response (one wrong histology, two never treated). Prior therapy was doxorubicin-based in 90%, and ifosfamide-based in 6%. The overall objective response rate is 27%, with complete response in 6.3% (3/48), and partial response in 20.8% (10/48). An additional 50% (24/48) had stable disease (median duration 5.4 months). The median number of cycles per patient was 5.5 (range 1-22); 73% of patients remained progression-free at 12 weeks and 52% at 24 weeks. The predominant toxicity was uncomplicated myelosuppression: thrombocytopenia grade 3 (29%), grade 4 (10.4%); neutropenia grade 3 (12.5%), grade 4 (8.3%) anemia grade 3 (20.8%), grade 4 (4.2%). While pulmonary toxicity was reported, no patient had drug-related pneumonitis/hypoxia-type toxicity. Median progression-free survival (PFS) was 5. 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. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript months (range 0.7 -27+ months). The median duration of objective response was 9+ months (range 3.9 -24.5+ months).Conclusion-Fixed-dose rate gemcitabine plus docetaxel is active second-line therapy for uterine leiomyosarcoma.

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Section: Introductionmentioning

confidence: 99%

Fixed-dose rate gemcitabine plus docetaxel as second-line therapy for metastatic uterine leiomyosarcoma: A Gynecologic Oncology Group phase II study

Hensley

Blessing

Mannel

et al. 2008

Gynecologic Oncology

243

133

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“…Of the 6 studied agents, only the study of thalidomide (229-B) has been published, showing minimal activity, with 8% of patients remaining progression-free at 6 months. 9 In ovarian cancer treatment, the concept of the platinum-free interval exists as a marker for prognosis after recurrence. 10,11 In recurrent ovarian cancer management, the platinum-free interval is used to distinguish dichotomous groups of patients based on prognoses and probability of response to salvage agents.…”

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confidence: 99%

Does the progression‐free interval after primary chemotherapy predict survival after salvage chemotherapy in advanced and recurrent endometrial cancer?

Moore

Tian

McMeekin

et al. 2010

Cancer

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BACKGROUND: This study evaluated whether progression-free interval (PFI) following primary chemotherapy (PCT) was predictive of overall survival (OS) after second-line chemotherapy in advanced/recurrent endometrial cancer (EC). METHODS: This is a pooled analysis of patients who recurred after PCT and were treated with second-line chemotherapy on Gynecologic Oncology Group trials. PFI-1 measured from initiation of PCT to recurrence or treatment-free interval (TFI) measured from completion of PCT to initiation of second-line chemotherapy was evaluated in relation to clinical outcomes. RESULTS: A total of 586 patients treated on 5 phase 3 PCT protocols were included. Baseline factors in primary setting associated with clinical outcome after PCT were also predictive of OS after second-line chemotherapy, including race, Gynecologic Oncology Group performance status, grade, and prior radiation therapy (P < .01). PFI-1 was the most significant factor predictive of survival after second-line chemotherapy, with a 30% reduction in the risk of death for PFI-1 >6 months compared with 6 months (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.59-0.84 [P < .0001]) and median OS after second-line chemotherapy of 10 versus 5 months. A total of 275 patients treated on 9 phase 2 second-line chemotherapy protocols were also evaluated, and TFI >3 months was associated with a 25% reduction in the risk of death (HR, 0.75; 95% CI,) and median OS after second-line chemotherapy of 10 versus 7 months compared with TFI 3 months. The tumor response to second-line chemotherapy was 9.6% versus 5.8%; the difference was not statistically significant. CONCLUSIONS: Time to recurrence after PCT is predictive of survival after recurrence in advanced/recurrent EC. However, there is no evidence that this variable can be used in selecting salvage chemotherapy.

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“…thalidomide alone is not effective in the treatment of metastasic breast cancer, and must be combined with another cytotoxic drug or an alternative therapy (23). While thalidomide is found to be cytotoxic Figure 2.…”

Section: Discussionmentioning

confidence: 99%

Thalidomide and irradiation combination therapy increases substance P levels in vitro

Aydemir

Korcum

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. thalidomide is an anti-angiogenic agent that is used in the treatment of cancer. however, in many cases, particularly in patients with breast cancer, thalidomide treatment alone is insufficient and must be combined with other drugs or therapies. in the clinical setting, thalidomide is most commonly used in combination with radiation therapy. however, the exact mechanisms of its effect are unkown. radiotherapy alters the expression of substance p, which is considered a crucial pro-angiogenic peptide. to determine whether thalidomide and radiotherapy in combination overcome the limitations of each as monotherapy, we examined the effects of the combination on the growth of breast cancer cells as well as on the expression of substance p in vitro. mouse breast cancer cells (4t1) and cells produced from metastatic lesions (4thmpc) were treated with radiotherapy (rt) (45 Gy) alone, thalidomide (thal) (40 µg/ml) alone or combination therapy (40 µg/ml thal + 45 Gy rt), and compared with control cells. mtS, live/dead and trypan blue exclusion assays were used to evaluate the cytotoxic effects of the treatments. the levels of substance p in the conditioned media and in the cell lysates were determined by a substance p EliSa kit, and changes in the protein content were analyzed by Western blotting. Thalidomide alone resulted in a significant inhibition in the growth of the 4t1 (34.1%) and 4thmpc (52.6%) cell lines. rt alone inhibited the growth of the 4t1 (19.2%) and 4thmpc (23.31%) cell lines. the combination therapy enhanced the growth inhibition noted in the 4t1 (47.9%) and 4thmpc (62.03%) cell lines. the expression of substance p in the conditioned media and in the cell lysates increased within 72 h of RT. This increase was significantly enhanced with the combination therapy. these data indicate that thalidomide inhibits breast cancer cell growth and potentiates the anti-tumor effects of radiation at appropriate doses.

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

Cited by 87 publications

References 42 publications

Fixed-dose rate gemcitabine plus docetaxel as second-line therapy for metastatic uterine leiomyosarcoma: A Gynecologic Oncology Group phase II study

Fixed-dose rate gemcitabine plus docetaxel as second-line therapy for metastatic uterine leiomyosarcoma: A Gynecologic Oncology Group phase II study

Does the progression‐free interval after primary chemotherapy predict survival after salvage chemotherapy in advanced and recurrent endometrial cancer?

Thalidomide and irradiation combination therapy increases substance P levels in vitro

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