A Phase II Trial of Topotecan in Patients with Advanced, Persistent, or Recurrent Endometrial Carcinoma: A Gynecologic Oncology Group Study

Miller, David S.; Blessing, John A.; Lentz, Samuel S.; Waggoner, Steven

doi:10.1006/gyno.2002.6804

Cited by 88 publications

(32 citation statements)

References 23 publications

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“…Patients enrolled in these studies were reviewed to determine whether the treatment-free interval (TFI) can be used to predict tumor response, PFS, and OS from time of second-line chemotherapy. [6][7][8][15][16][17][18][19][20] Eligibility criteria were similar for all Gynecologic Oncology Group 129 series studies. Patients were required to have recurrent or persistent endometrial carcinoma refractory to curative therapy with established treatments.…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, if one considers 6-month PFS as the endpoint of interest for these studies with a cutoff of >20% warranting further evaluation, then the following agents would have been advanced: paclitaxel (6-month PFS, 21%), Doxil (23%), topotecan (25%), oxaliplatin (27%), and irofulven (28%). [6][7][8]18,19 This is compared with success based on RR, where only paclitaxel was approved for further study. In patients with terminal disease, deciding on an appropriate study outcome may change how we interpret success in these protocols.…”

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confidence: 99%

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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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Section: Methodsmentioning

confidence: 99%

mentioning

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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“…Paclitaxel has performed the best, with response rates consistently greater than 20%, although these data predate the use of paclitaxel as a part of first-line treatment [53][54][55][56]. Other agents tested but demonstrating limited response rates include oxaliplatin, topotecan, liposomal doxorubicin, etoposide, cyclophosphamide, pemetrexed, gemcitabine, and ifosfamide [57][58][59][60][61][62][63][64][65] (Table 4).…”

Section: Second-line Chemotherapymentioning

confidence: 99%

Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings

Bestvina

Fleming

2016

The Oncologist

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Level I evidence exists for use of adjuvant chemotherapy in stage IIIC endometrial cancer (positive lymph nodes), although results of randomized trials have varied. Chemotherapy is also often recommended for high-risk subsets of stage I disease, such as serous carcinomas, although prospective trial data to validate this practice are lacking. Carboplatin plus paclitaxel is the current standard regimen, based on extrapolation of data from the metastatic setting. Several clinical trials have compared adjuvant pelvic radiotherapy alone to a combination of radiotherapy and chemotherapy with mixed results. One of the largest of these trials, Postoperative Radiation Therapy in Endometrial Carcinoma 3 (PORTEC-3), has completed accrual and is awaiting data maturation. Metastatic disease is not curable. For tumors of low-grade endometrioid histology with a prolonged time to recurrence, endocrine therapy with a progestin-based regimen is appropriate. Chemotherapy will be used in most other cases, and the standard first-line regimen is carboplatin and paclitaxel. Few chemotherapy agents have been shown to produce meaningful response rates in the second-line setting. Molecularly targeted therapies such as mTOR inhibitors and antiangiogenic agents including bevacizumab have been studied but their role in the armamentarium remains uncertain. The Oncologist 2016; 21:1250-1259 Implications for Practice: Following surgical resection and staging for endometrial cancer, adjuvant chemotherapy with carboplatin and paclitaxel can be administered to patients with a high risk for recurrence. This includes patients with stage IIIC disease with positive lymph nodes, and high-risk subsets of stage I disease such as serous carcinomas. In the metastatic setting, endocrine therapy can be considered, particularly for patients with lower-grade disease and a prolonged time to recurrence. Combined therapy with carboplatin and paclitaxel is the standard of care used for front-line chemotherapy. Antiangiogenic agents are clearly active, but how they should be integrated into treatment is not yet determined. Immunotherapy is a promising direction for patients with mismatch repair-deficient or polymerase «-mutated tumors.

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“…Investigations performed on neuroblastoma cell lines indicated that topotecan was able to inhibit not only hypoxia-induced but also IGF-Iinduced VEGF expressions showing multi-directional blocking activity (Beppu et al 2005). Besides neuroblastoma, topotecan has revealed limited activity as a second line therapy for advanced or recurrent endometrial cancer; however, some patients suffered from severe and potentially fatal toxicities (Miller et al 2002). Some in vitro studies seem to confirm that higher topotecan efficacy is obtained only in subtoxic or toxic doses (Brown et al 2006).…”

Section: Inhibitors Of Hif-1 Activation and Hif-1-dependent Pathwaysmentioning

confidence: 99%

Targeting NF-κB and HIF-1 Pathways for the Treatment of Cancer: Part II

Wilczyński

Duechler

Czyż

2011

Arch. Immunol. Ther. Exp.

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Hypoxia that originates from disturbed growth of solid tumors initiates a cascade of intracellular events engaging hypoxia-inducible factors, HIF-1 and HIF-2. Overexpression of HIF has been confirmed in solid tumors and was unfortunately accompanied with chemo- and radioresistance observed in many patients. Multiple cellular pathways resulting in HIF activation could be successfully inhibited by use of different kinds of drugs (e.g. topotecan, heat shock protein 90 and mTOR inhibitors, YC-1, pleurotin or 2-methoxyestradiol), which are being subjected into intensive investigation in clinical trials.

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A Phase II Trial of Topotecan in Patients with Advanced, Persistent, or Recurrent Endometrial Carcinoma: A Gynecologic Oncology Group Study

Cited by 88 publications

References 23 publications

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

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

Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings

Targeting NF-κB and HIF-1 Pathways for the Treatment of Cancer: Part II

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