A phase II trial of weekly 1-hour paclitaxel as second-line therapy for endometrial and cervical cancer

Homesley, Howard D.; Meltzer, Nathan P.; Nieves, Lucybeth; Vaccarello, Luis; Lowendowski, G.; Elbendary, Alaa

doi:10.1007/s10147-007-0731-5

Cited by 27 publications

(12 citation statements)

References 24 publications

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“…The majority of the data for second-line chemotherapy come from nonrandomized phase II trials in patients whose prior chemotherapy was in the setting of metastatic disease. 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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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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“…The data for weekly paclitaxel in recurrent endometrial cancer is limited, however phase II studies report a response rate of 26.7% (among patients who had received paclitaxel as front line therapy (73%)). [47] Rational combination studies may help us identify superior treatment strategies. With current strategies of enrolling unselected patients to single agent biologics, we may continue to struggle to identify agents with possible benefit.…”

Section: Discussionmentioning

confidence: 99%

A phase II trial of trebananib (AMG 386; IND#111071), a selective angiopoietin 1/2 neutralizing peptibody, in patients with persistent/recurrent carcinoma of the endometrium: An NRG/Gynecologic Oncology Group trial

Moore

Sill

Tenney

et al. 2015

Gynecologic Oncology

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Objectives Ang1&2 (angiopoietin-1; -2) interact with Tie2 receptors on endothelial cells to mediate vascular remodeling in an angiogenesis signaling pathway distinct from the VEGF axis. Trebaninib is a peptide Fc fusion protein that binds Ang1 and 2 and prevents interaction with Tie2. The efficacy of trebananib in recurrent/persistent endometrial cancer (EC) was studied. Methods The primary objective was to determine the frequency of patients with objective tumor responses (ORR) and event-free survival for ≥6 months (6-month EFS) and determine toxicity of trebananib at a dose and schedule of 15mg/kg, IV QW. Recurrent/persistent EC, measurable disease, and ≤2 prior chemotherapy lines were required. Results Thirty-two patients were eligible and treated. The most common histologies were G1/2 endometrioid (31%), G3 endometrioid (28%) and serous (31.3%). 78% of patients had 1 prior regimen. Patients received 1-9+ cycles of trebananib; 24 patients (75%) received ≤2 cycles. One patient had a partial response (3.1%); 8 patients had stable disease (25%) and 5 patients (15.6%) had 6 month EFS. Median progression-free survival and overall-survival were 1.97 months (90% CI 1.77-2.1) and 6.6 months (90% CI 4.01-14.75), respectively. Most common adverse events (AE) were fatigue, anemia, and GI issues. Grade 3 and 4 AEs were: GI 31 and 0%; Vascular 22 and 0%; Metabolism/nutrition 19 and 3%; General (including edema) 16 and 0%. Conclusions Trebananib has insufficient single agent activity in recurrent EC to warrant further investigation at this dose/schedule.

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“…21,22 Although a myriad of other cytotoxic agents have been investigated in the second-line setting, including cisplatin (RR, 4%), weekly docetaxel (RR, 7.7%), ixabepilone (RR, 12%), pegylated liposomal doxorubicin (RR, 19.5%), nonpegylated doxorubicin (RR, 0%), pemetrexed (RR, 4%), dactinomycin (RR, 12%), gemcitabine (RR, 4%), topotecan (RR, 9%), ifosfamide (RR, 15%), and oxaliplatin (RR, 13.5%), none have revealed positive results. 6Y12,23Y26…”

Section: Discussionmentioning

confidence: 99%

Treatment of Advanced or Recurrent Endometrial Carcinoma With Doxorubicin in Patients Progressing After Paclitaxel/Carboplatin

Makker

Hensley

Zhou

et al. 2013

International Journal of Gynecological Cancer

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Objective Long-term survival for patients with advanced endometrial carcinoma is poor, and limited options exist for the management of recurrent disease. Our goal was to investigate the activity of doxorubicin in the second-line setting in patients who progressed after paclitaxel/carboplatin adjuvant treatment. Methods We conducted a retrospective analysis of patients with recurrent endometrial carcinoma who were treated at Memorial Sloan-Kettering Cancer Center from 1995-2009, and who received paclitaxel/carboplatin adjuvant chemotherapy followed by second-line doxorubicin therapy at time of recurrence. The median PFS and OS times following paclitaxel/carboplatin and following second-line doxorubicin therapy were estimated using the Kaplan-Meier method. Toxicity was assessed by the treating physician at each visit and graded using version 4.0 of Common Terminology Criteria for Adverse Events (CTCAE). Patient presentation, treatment, patterns of recurrence, and patient outcomes were summarized. Results Seventeen patients were included in study analyses. The median PFS from completion of paclitaxel/carboplatin was 8.0 months (95% CI: 4.5-13.6 months). At the time of recurrence, all 17 patients were treated with doxorubicin as second-line therapy. No patient achieved objective response of stable disease. The median PFS of this cohort following doxorubicin treatment was 2.1 months (95% CI: 0.95-2.7) months. Median OS was 5.8 months (95% CI: 1.0-15.0 months). There is only one patient still alive; her median follow-up time is 49.4 months. Predominant doxorubicin-related grade 2 toxicities included nausea/vomiting (18.8%), fatigue (18.8%), and neutropenia (12.5%). No grade 3 or 4 toxicities occurred. Conclusions Among patients with advanced endometrial carcinoma who had received adjuvant paclitaxel/carboplatin, treatment with doxorubicin at time of disease recurrence failed to achieve any objective responses and was associated with a very short (2 months) time to progression. Doxorubicin may be considered inactive as second-line therapy in this endometrial carcinoma population.

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A phase II trial of weekly 1-hour paclitaxel as second-line therapy for endometrial and cervical cancer

Abstract: Although confirmatory larger trials are needed, weekly paclitaxel appears promising for advanced endometrial carcinoma, and possibly for squamous cell carcinoma of the cervix.

Cited by 27 publications

References 24 publications

Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings

Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings

A phase II trial of trebananib (AMG 386; IND#111071), a selective angiopoietin 1/2 neutralizing peptibody, in patients with persistent/recurrent carcinoma of the endometrium: An NRG/Gynecologic Oncology Group trial

Treatment of Advanced or Recurrent Endometrial Carcinoma With Doxorubicin in Patients Progressing After Paclitaxel/Carboplatin

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