Abstract
Original language | English |
---|---|
Pages (from-to) | 565-571 |
Number of pages | 7 |
Journal | British Journal of Cancer |
Volume | 119 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2018 |
Keywords
- alanine aminotransferase
- anthracycline
- aspartate aminotransferase
- creatinine
- dexamethasone
- docetaxel
- gemcitabine
- hemoglobin
- ifosfamide
- trabectedin
- abdominal hysterectomy
- abdominal pain
- adjuvant radiotherapy
- adult
- advanced cancer
- aged
- allergic reaction
- anorexia
- Article
- atrial fibrillation
- cancer combination chemotherapy
- cancer diagnosis
- cancer fatigue
- cancer localization
- cancer pain
- cancer prognosis
- cancer radiotherapy
- cancer recurrence
- cancer staging
- cancer surgery
- cholecystitis
- colon obstruction
- constipation
- controlled study
- dermatitis
- diarrhea
- drug efficacy
- drug safety
- dyspnea
- enteritis
- external beam radiotherapy
- extravasation
- female
- fever
- fistula
- human
- hydronephrosis
- hyperglycemia
- hyponatremia
- infusion related reaction
- intestine perforation
- liver toxicity
- lung embolism
- lymph node dissection
- major clinical study
- metastasis
- multicenter study
- multimodality cancer therapy
- multiple cycle treatment
- nausea and vomiting
- null hypothesis
- patient history of chemotherapy
- peripheral edema
- phase 2 clinical trial
- priority journal
- progression free survival
- randomized controlled trial
- rectum perforation
- salpingooophorectomy
- sensory neuropathy
- side effect
- single blind procedure
- treatment interruption
- treatment planning
- urogenital tract disease
- uterus sarcoma
- vein thrombosis
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A phase II randomised (calibrated design) study on the activity of the single-agent trabectedin in metastatic or locally relapsed uterine leiomyosarcoma. / Gadducci, A.; Grosso, F.; Scambia, G. et al.
In: British Journal of Cancer, Vol. 119, No. 5, 2018, p. 565-571.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - A phase II randomised (calibrated design) study on the activity of the single-agent trabectedin in metastatic or locally relapsed uterine leiomyosarcoma
AU - Gadducci, A.
AU - Grosso, F.
AU - Scambia, G.
AU - Raspagliesi, F.
AU - Colombo, N.
AU - Grignani, G.
AU - Casali, P.
AU - Sanfilippo, R.
AU - Buonadonna, A.
AU - Santoro, A.
AU - Bruzzone, M.
AU - Artioli, G.
AU - Lorusso, D.
AU - Biagioli, E.
AU - Fossati, R.
AU - Galli, F.
AU - Negri, E.
AU - Rulli, E.
AU - Torri, V.
AU - D’Incalci, M.
N1 - Export Date: 5 February 2019 CODEN: BJCAA Correspondence Address: Fossati, R.; IRCCS – Mario Negri Institute for Pharmacological ResearchItaly; email: roldano.fossati@marionegri.it Chemicals/CAS: alanine aminotransferase, 9000-86-6, 9014-30-6; aspartate aminotransferase, 9000-97-9; creatinine, 19230-81-0, 60-27-5; dexamethasone, 50-02-2; docetaxel, 114977-28-5; gemcitabine, 103882-84-4; hemoglobin, 9008-02-0; ifosfamide, 3778-73-2; trabectedin, 114899-77-3 Funding text 1: Funding: Funding for this study has been provided by IRCCS Mario Negri Institute, Milan, Italy and partial unconditional funding from Pharma Mar. References: Toro, J.R., Incidence patterns of soft tissue sarcomas, regardless of primary site, in the surveillance, epidemiology and end results program, 1978-2001: an analysis of 26,758 cases (2006) Int J. Cancer, 119, pp. 2922-2930. , COI: 1:CAS:528:DC%2BD28Xht1yqt7nP; Major, F.J., Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study (1993) Cancer, 71, pp. 1702-1709. , COI: 1:STN:280:DyaK3s7mtFeisg%3D%3D; Gadducci, A., Prognostic factors in uterine sarcoma (2011) Best Pract. Res Clin. Obstet. Gynaecol., 25, pp. 783-795; Gadducci, A., Uterine leiomyosarcoma: analysis of treatment failures and survival (1996) Gynecol. Oncol., 62, pp. 25-32. , COI: 1:STN:280:DyaK283ps1SitQ%3D%3D; El-Khalfaoui, K., Current and future options in the management and treatment of uterine sarcoma (2014) Ther. Adv. Med Oncol., 6, pp. 21-28; Bartosch, C., Distant metastases in uterine leiomyosarcomas: the wide variety of body sites and time intervals to metastatic relapse (2017) Int J. Gynecol. Pathol., 36, pp. 31-41. , COI: 1:CAS:528:DC%2BC28XitVyrsb7F; Gadducci, A., Cosio, S., Romanini, A., Genazzani, A.R., The management of patients with uterine sarcoma: a debated clinical challenge (2008) Crit. Rev. Oncol. Hematol., 65, pp. 129-142; Amant, F., Coosemans, A., Debiec-Rychter, M., Timmerman, D., Vergote, I., Clinical management of uterine sarcomas (2009) Lancet Oncol., 10, pp. 1188-1198; Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2014) Ann. Oncol. J. Eur. Soc. Med Oncol., 25, pp. iii102-iii112; Leitao, M.M., Surgical resection of pulmonary and extrapulmonary recurrences of uterine leiomyosarcoma (2002) Gynecol. Oncol., 87, pp. 287-294; Burt, B.M., Repeated and aggressive pulmonary resections for leiomyosarcoma metastases extends survival (2011) Ann. Thorac. Surg., 92, pp. 1202-1207; Gupta, A.A., Yao, X., Verma, S., Mackay, H., Hopkins, L., Systematic Chemotherapy for Inoperable, Locally Advanced, Recurrent, or Metastatic Uterine Leiomyosarcoma: A Systematic Review (2013) Clinical Oncology, 25 (6), pp. 346-355. , COI: 1:STN:280:DC%2BC3s3ntlentA%3D%3D; Paik, E.S., Pulmonary metastasectomy in uterine malignancy: outcomes and prognostic factors (2015) J. Gynecol. Oncol., 26, pp. 270-276. , COI: 1:CAS:528:DC%2BC1cXmsVWmu7s%3D; Look, K.Y., Sandler, A., Blessing, J.A., Lucci, J.A., Rose, P.G., Phase II trial of gemcitabine as second-line chemotherapy of uterine leiomyosarcoma: a Gynecologic Oncology Group (GOG) Study (2004) Gynecologic Oncology, 92 (2), pp. 644-647. , COI: 1:CAS:528:DC%2BD2cXptV2quw%3D%3D; Hensley, M.L., Blessing, J.A., Mannel, R., Rose, P.G., Fixed-dose rate gemcitabine plus docetaxel as first-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II trial (2008) Gynecol. Oncol., 109, pp. 329-334. , COI: 1:CAS:528:DC%2BD1cXmvVKrsLw%3D; Hensley, M.L., Fixed-dose rate gemcitabine plus docetaxel as second-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II study (2008) Gynecol. Oncol., 109, pp. 323-328. , COI: 1:CAS:528:DC%2BD1cXmvVKrsL8%3D; Tap, W.D., Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial (2016) Lancet Lond. Engl., 388, pp. 488-497. , COI: 1:CAS:528:DC%2BC28Xps12iu7Y%3D; Fayette, J., ET-743: a novel agent with activity in soft-tissue sarcomas (2006) Curr. Opin. Oncol., 18, pp. 347-353. , COI: 1:CAS:528:DC%2BD28XkvVWltbY%3D; D’Incalci, M., Galmarini, C.M., A review of trabectedin (ET-743): a unique mechanism of action (2010) Mol. Cancer Ther., 9, pp. 2157-2163; Allavena, P., Anti-inflammatory properties of the novel antitumor agent yondelis (trabectedin): inhibition of macrophage differentiation and cytokine production (2005) Cancer Res., 65, pp. 2964-2971. , COI: 1:CAS:528:DC%2BD2MXjtVeqtL8%3D; Germano, G., Role of macrophage targeting in the antitumor activity of trabectedin (2013) Cancer Cell., 23, pp. 249-262. , COI: 1:CAS:528:DC%2BC3sXisVSqtbs%3D; Germano, G., Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells (2010) Cancer Res., 70, pp. 2235-2244. , COI: 1:CAS:528:DC%2BC3cXjtFygt78%3D; Mantovani, A., Marchesi, F., Malesci, A., Laghi, L., Allavena, P., Tumour-associated macrophages as treatment targets in oncology (2017) Nat. Rev. Clin. Oncol., 14, pp. 399-416. , COI: 1:CAS:528:DC%2BC2sXhsFGlsbs%3D; Lee, C.H., Prognostic significance of macrophage infiltration in leiomyosarcomas (2008) Clin. Cancer Res., 14, pp. 1423-1430. , COI: 1:CAS:528:DC%2BD1cXislSrsL0%3D; D’Incalci, M., Badri, N., Galmarini, C.M., Allavena, P., Trabectedin, a drug acting on both cancer cells and the tumour microenvironment (2014) Br. J. Cancer, 111, pp. 646-650; Grosso, F., Steroid premedication markedly reduces liver and bone marrow toxicity of trabectedin in advanced sarcoma (2006) Eur. J. Cancer, 42, pp. 1484-1490. , COI: 1:CAS:528:DC%2BD28XlvF2jsb0%3D; Monk, B.J., Trabectedin as a chemotherapy option for patients with BRCA deficiency (2016) Cancer Treat. Rev., 50, pp. 175-182. , COI: 1:CAS:528:DC%2BC28XhsFemsr%2FF; Casado, J.A., Relevance of the Fanconi anemia pathway in the response of human cells to trabectedin (2008) Mol. Cancer Ther. maggio, 7, pp. 1309-1318. , COI: 1:CAS:528:DC%2BD1cXlvFams7s%3D; Maki, R.G., Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of Sarcoma Alliance for Research Through Collaboration Study 002 (2007) J. Clin. Oncol., 25, pp. 2755-2763. , COI: 1:CAS:528:DC%2BD2sXosValtLY%3D; Grosso, F., Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study (2007) Lancet Oncol., 8, pp. 595-602. , COI: 1:CAS:528:DC%2BD2sXnsFKkur0%3D; Tewari, D., Activity of trabectedin (ET-743, Yondelis) in metastatic uterine leiomyosarcoma (2006) Gynecol. Oncol., 102, pp. 421-424. , COI: 1:CAS:528:DC%2BD28Xps1Wms7c%3D; Amant, F., Coosemans, A., Renard, V., Everaert, E., Vergote, I., Clinical outcome of ET-743 (Trabectedin; Yondelis) in high-grade uterine sarcomas: report on five patients and a review of the literature (2009) Int J. Gynecol. Cancer, 19, pp. 245-248; Sanfilippo, R., Trabectedin in advanced uterine leiomyosarcomas: a retrospective case series analysis from two reference centers (2011) Gynecol. Oncol., 123, pp. 553-556. , COI: 1:CAS:528:DC%2BC3MXhsVOisrzO; Hensley, M.L., Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: subgroup analysis of a phase 3, randomized clinical trial (2017) Gynecol. Oncol., 146, pp. 531-537. , COI: 1:CAS:528:DC%2BC2sXhtVGms7nM; Judson, I.R., Trabectedin (Tr) in the treatment of advanced uterine leiomyosarcomas (U-LMS): results of a pooled analysis of five single-agent phase II studies using the recommended dose (2010) J. Clin. Oncol., 28, p. 10028; Van Glabbeke, M., Verweij, J., Judson, I., Nielsen, O.S., Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas (2002) Eur. J. Cancer, 38, pp. 543-549; A’Hern, R.P., Sample size tables for exact single-stage phase II designs (2001) Stat. Med., 20, pp. 859-866; Pautier, P., Trabectedin in combination with doxorubicin for first-line treatment of advanced uterine or soft-tissue leiomyosarcoma (LMS-02): a non-randomised, multicentre, phase 2 trial (2015) Lancet Oncol., 16, pp. 457-464. , COI: 1:CAS:528:DC%2BC2MXkvVWgsbw%3D; Martin-Broto, J., Randomized phase II study of trabectedin and doxorubicin compared with doxorubicin alone as first-line treatment in patients with advanced soft tissue sarcomas: a Spanish Group for Research on Sarcoma Study (2016) J. Clin. Oncol., 34, pp. 2294-2302. , COI: 1:CAS:528:DC%2BC2sXhsFGlt7fP; Pautier, P., Randomized multicenter and stratified phase II study of gemcitabine alone versus gemcitabine and docetaxel in patients with metastatic or relapsed leiomyosarcomas: a Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) French Sarcoma Group Study (TAXOGEM study) (2012) Oncologist, 17, pp. 1213-1220. , COI: 1:CAS:528:DC%2BC38XhslSktrrL; Herson, J., Carter, S.K., Calibrated phase II clinical trials in oncology (1986) Stat. Med., 5, pp. 441-447. , COI: 1:STN:280:DyaL2s%2FmvFWruw%3D%3D
PY - 2018
Y1 - 2018
N2 - Background: Patients with recurrent/metastatic uterine leiomyosarcoma (U-LMS) have a dismal prognosis. This phase II study aims to evaluate trabectedin efficacy and safety in advanced U-LMS. Methods: Eligible patients had received ≥ one line of chemotherapy. Gemcitabine ± docetaxel naive patients were randomised to Arm A: trabectedin 1.3 mg/m2 or calibration Arm B: gemcitabine 900 mg/m2 and docetaxel 75 mg/m2. Patients who had already received gemcitabine ± docetaxel directly entered Arm A. Primary end-point: 6-month progression-free rate (PFS-6). The null hypothesis that the true PFS-6 = 14% was tested against a one-sided alternative. This design yielded a 5% type I error rate and 90% power when the true PFS-6 is 25%. Results: Overall, 126 patients entered Arm A (45 from randomisation and 81 directly) and 42 Arm B. Arm A patients characteristics: median age = 57; ≥2 previous chemotherapy lines = 37.4%; metastatic disease = 93%. The study met the condition for trabectedin activity: PFS-6 = 35.2% (95% CI: 26.2–45). No difference in PFS by the number of previous chemotherapy lines emerged. Median OS = 20.6 months (IQR: 8–36.4). In Arm B, the PFS-6 = 51.5% (95% CI: 33.5–69.2). No toxic deaths occurred. In Arm A, only 4 patients interrupted treatment for toxicity. Conclusions: Trabectedin is active and well tolerated, retaining similar efficacy across one to three previous lines of chemotherapy. © 2018, Cancer Research UK.
AB - Background: Patients with recurrent/metastatic uterine leiomyosarcoma (U-LMS) have a dismal prognosis. This phase II study aims to evaluate trabectedin efficacy and safety in advanced U-LMS. Methods: Eligible patients had received ≥ one line of chemotherapy. Gemcitabine ± docetaxel naive patients were randomised to Arm A: trabectedin 1.3 mg/m2 or calibration Arm B: gemcitabine 900 mg/m2 and docetaxel 75 mg/m2. Patients who had already received gemcitabine ± docetaxel directly entered Arm A. Primary end-point: 6-month progression-free rate (PFS-6). The null hypothesis that the true PFS-6 = 14% was tested against a one-sided alternative. This design yielded a 5% type I error rate and 90% power when the true PFS-6 is 25%. Results: Overall, 126 patients entered Arm A (45 from randomisation and 81 directly) and 42 Arm B. Arm A patients characteristics: median age = 57; ≥2 previous chemotherapy lines = 37.4%; metastatic disease = 93%. The study met the condition for trabectedin activity: PFS-6 = 35.2% (95% CI: 26.2–45). No difference in PFS by the number of previous chemotherapy lines emerged. Median OS = 20.6 months (IQR: 8–36.4). In Arm B, the PFS-6 = 51.5% (95% CI: 33.5–69.2). No toxic deaths occurred. In Arm A, only 4 patients interrupted treatment for toxicity. Conclusions: Trabectedin is active and well tolerated, retaining similar efficacy across one to three previous lines of chemotherapy. © 2018, Cancer Research UK.
KW - alanine aminotransferase
KW - anthracycline
KW - aspartate aminotransferase
KW - creatinine
KW - dexamethasone
KW - docetaxel
KW - gemcitabine
KW - hemoglobin
KW - ifosfamide
KW - trabectedin
KW - abdominal hysterectomy
KW - abdominal pain
KW - adjuvant radiotherapy
KW - adult
KW - advanced cancer
KW - aged
KW - allergic reaction
KW - anorexia
KW - Article
KW - atrial fibrillation
KW - cancer combination chemotherapy
KW - cancer diagnosis
KW - cancer fatigue
KW - cancer localization
KW - cancer pain
KW - cancer prognosis
KW - cancer radiotherapy
KW - cancer recurrence
KW - cancer staging
KW - cancer surgery
KW - cholecystitis
KW - colon obstruction
KW - constipation
KW - controlled study
KW - dermatitis
KW - diarrhea
KW - drug efficacy
KW - drug safety
KW - dyspnea
KW - enteritis
KW - external beam radiotherapy
KW - extravasation
KW - female
KW - fever
KW - fistula
KW - human
KW - hydronephrosis
KW - hyperglycemia
KW - hyponatremia
KW - infusion related reaction
KW - intestine perforation
KW - liver toxicity
KW - lung embolism
KW - lymph node dissection
KW - major clinical study
KW - metastasis
KW - multicenter study
KW - multimodality cancer therapy
KW - multiple cycle treatment
KW - nausea and vomiting
KW - null hypothesis
KW - patient history of chemotherapy
KW - peripheral edema
KW - phase 2 clinical trial
KW - priority journal
KW - progression free survival
KW - randomized controlled trial
KW - rectum perforation
KW - salpingooophorectomy
KW - sensory neuropathy
KW - side effect
KW - single blind procedure
KW - treatment interruption
KW - treatment planning
KW - urogenital tract disease
KW - uterus sarcoma
KW - vein thrombosis
U2 - 10.1038/s41416-018-0190-y
DO - 10.1038/s41416-018-0190-y
M3 - Article
VL - 119
SP - 565
EP - 571
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 5
ER -