Regular ArticleA Phase II Trial of Paclitaxel in Patients with Advanced or Recurrent Adenocarcinoma of the Endometrium: A Gynecologic Oncology Group Study☆
Abstract
Objective: To determine the efficacy and toxicity of paclitaxel in advanced or recurrent adenocarcinoma of the endometrium. Methods: Thirty patients with advanced or recurrent endometrial cancer with measurable disease not previously treated with chemotherapy were treated with paclitaxel, 250 mg/m2, over 24 hr with G-CSF, 5 mcg/kg/day, from Days 2 to 12. The cycle was repeated every 21 days. Patients who had received previous pelvic radiation were treated at an initial paclitaxel dose of 200 mg/m2. Twenty-eight patients were evaluable for response, and 29 patients for toxicity. All patients were Gynecologic Oncology Group performance status 0, 1, or 2. Results: Complete responses were observed in 4 (14.3%) and partial responses in 6 patients (21.4%) for a response rate of 35.7%. Severe (grade 3 or 4) leukopenia or thrombocytopenia was seen in 18 and 2 patients, respectively. Grade 3 or 4 gastrointestinal toxicity was seen in 5, neurotoxicity in 3, anemia in 2, and cardiac toxicity in 1 patients. Alopecia was reported in 16 patients. Conclusions: This dose and schedule of paclitaxel are active in patients with advanced or recurrent adenocarcinoma of the endometrium and should be considered for inclusion in phase III trials.
References (0)
Cited by (224)
A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer
2023, Gynecologic OncologyThis phase 2 study investigated sapanisertib (selective dual inhibitor of mTORC1/2) alone, or in combination with paclitaxel or TAK-117 (a selective small molecule inhibitor of PI3K), versus paclitaxel alone in advanced, recurrent, or persistent endometrial cancer.
Patients with histologic diagnosis of endometrial cancer (1–2 prior regimens) were randomized to 28-day cycles on four treatment arms: 1) weekly paclitaxel 80 mg/m2 (days 1, 8, and 15); 2) weekly paclitaxel 80 mg/m2 + oral sapanisertib 4 mg on days 2–4, 9–11, 16–18, and 23–25; 3) weekly sapanisertib 30 mg, or 4) sapanisertib 4 mg + TAK-117 200 mg on days 1–3, 8–10, 15–17, and 22–24.
Of 241 patients randomized, 234 received treatment (paclitaxel, n = 87 [3 ongoing]; paclitaxel+sapanisertib, n = 86 [3 ongoing]; sapanisertib, n = 41; sapanisertib+TAK-117, n = 20). The sapanisertib and sapanisertib+TAK-117 arms were closed to enrollment after futility analyses. After a median follow-up of 14.4 (paclitaxel) versus 17.2 (paclitaxel+sapanisertib) months, median progression-free survival (PFS; primary endpoint) was 3.7 versus 5.6 months (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.58–1.15; p = 0.139); in patients with endometrioid histology (n = 116), median PFS was 3.3 versus 5.7 months (HR 0.66; 95% CI 0.43–1.03). Grade ≥ 3 treatment-emergent adverse event rates were 54.0% with paclitaxel versus 89.5% paclitaxel+sapanisertib.
Our findings support inclusion of chemotherapy combinations with investigational agents for advanced or metastatic disease. The primary endpoint was not met and toxicity was manageable.
Trial registration: ClinicalTrials.gov number, NCT02725268
Adenocarcinoma of the uterine corpus and sarcomas of the uterus
2023, DiSaia and Creasman Clinical Gynecologic OncologyEndometrial cancer remains the only gynecologic malignancy with a rising incidence and mortality. Although diagnostic techniques have evolved modestly, the surgical management of endometrial cancer was transformed with incorporation of sentinel lymph node dissection paradigms. Furthermore, significant gains have been achieved in molecular characterization of endometrial cancer, with publication of The Cancer Genome Atlas (TCGA) endometrial and subsequent studies. Incorporation of molecular diagnostics has ushered in immunotherapy as an effective treatment strategy in select patients, with alternate targeted therapies emerging as promising options.
Progress in endometrial cancer: Contributions of the former Gynecologic Oncology Group
2020, Gynecologic OncologyFor over forty years, the Gynecologic Oncology Group drove progress in treating endometrial cancer. The first decades of investigation began with a meticulous prospective, surgicopathologic staging study that was the platform for development of all subsequent trials. The resultant statistical model of low risk, intermediate risk, and high-risk groups of patients led to trials where therapeutic modalities were best targeted at disease spread. A clear role for chemotherapy was established. It was realized that greater advances might be achieved with the advent of newer anti-neoplastic agents and these agents were subjected to extensive phase II testing. These agents later were integrated into comparison trials for advanced endometrial cancer. Multimodality therapy continues to show promise. Hormonal therapy was thoroughly investigated and led to combination hormonal therapy trials. Newer agents, including biologics are under active study, as well as the potential contribution of modern imaging techniques. Finally, GOG0210 established a repository of clinical specimens with detailed clinical and epidemiologic data from patients with surgically staged endometrial carcinoma. This should provide for a much greater understanding of molecular characteristics associated with risk of endometrial cancer recurrence, clinical and histological characteristics, and epidemiologic factors.
Carboplatin and paclitaxel: Role in the treatment of endometrial cancer
2020, A Theranostic and Precision Medicine Approach for Female-Specific CancersEndometrial cancer is a common type of cancer affecting women. It is the most common form of uterine cancer and originates from the endometrium often after menopause. Over the last 10 years, on an average 1.9% increase in mortality rate has been reported. Based on extent of severity endometrial cancer is classified into eight stages: IA, IB, II, IIIA, IIIB, IIIC, IVA, and IVB. The major risk factors leading to endometrial cancer are obesity, type 2 diabetes, not giving birth, breast cancer treatment with tamoxifen, estrogen hormone replacement therapy, polycystic ovarian syndrome (PCOS), abnormal metabolic conditions, and family history of the disease. The treatments available to cure endometrial cancer include surgery, radiation therapy, hormone therapy, chemotherapy, and targeted drug therapy. Carboplatin in combination with paclitaxel has been the most efficient and least toxic for chemotherapy. These drugs are also highly administered in several other cancer types because of their unique properties. Carboplatin, a derivative of cisplatin, is a less toxic and more stable compound. This drug is capable of causing alkylation leading to production of reactive platinum complexes that damage DNA. Paclitaxel, on the other hand, interacts with the microtubules of the cell and hyperstabilizes them. This disrupts the normal cell cycle allowing cells to undergo apoptosis. Although solo drug therapy induced a lower level of overall response rate, it increased significantly when administered in combination. Favorable results were also obtained when these two drugs were administered in conjunction with other forms of cancer therapy such as radiation, surgery, and hormone therapy.
Subacute toxicity and toxicokinetics study of DHP107, an oral paclitaxel formulation with once-weekly dosing in mice
2019, Regulatory Toxicology and PharmacologyDHP107, an oral formulation of paclitaxel, is effectively and systemically absorbed in intestinal endothelial cells. Although the in vivo efficacy of DHP107 has been reported, the potential toxicity of DHP107 has not been evaluated. Therefore, this study was conducted to evaluate the toxicity and toxicokinetics of DHP107 orally administered to ICR mice at 25, 50, and 100 mg/kg via once-weekly dosing for six weeks. DHP107-related clinical signs were observed in both sexes at 100 mg/kg. There were significant increases in the number of platelets and percentages of reticulocytes and basophils in male mice. Also in males, there was a significant decrease in the absolute and relative weights of testes, epididymides, kidneys, and heart. Relative spleen weights were significantly increased in males treated with doses ≥50 mg/kg which had histopathological correlates. These changes were reversible after a two-week recovery period with the exception of the findings in the reproductive organs. Systemic exposure to paclitaxel increased with DHP107 doses in single and multiple dosing with no marked differences between sexes. In conclusion, the target organs were determined to be the reproductive and hematopoietic organs in male mice, suggesting of sex difference and the NOAEL of DHP107 was established to be < 25 mg/kg for males and 50 mg/kg for females.
Adenocarcinoma of the uterine corpus
2018, Clinical Gynecologic Oncology
- ☆
Reprint requests should be addressed to GOG Administrative Office, Suite 1945, 1234 Market Street, Philadelphia, PA 19107.