INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line.

Humans Female Carboplatin Trabectedin Ovarian Neoplasms / drug therapy Platinum / therapeutic use Neoplasm Recurrence, Local / drug therapy Carcinoma, Ovarian Epithelial / drug therapy Doxorubicin Polyethylene Glycols Antineoplastic Combined Chemotherapy Protocols / adverse effects

Journal

British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635

Informations de publication

Date de publication:
04 2023
Historique:
received: 29 07 2022
accepted: 06 12 2022
revised: 30 11 2022
medline: 5 4 2023
pubmed: 10 2 2023
entrez: 9 2 2023
Statut: ppublish

Résumé

This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. ClinicalTrials.gov, number NCT01379989.

Sections du résumé

BACKGROUND
This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC).
METHODS
Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75).
RESULTS
The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP).
CONCLUSIONS
This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, number NCT01379989.

Identifiants

DOI: 10.1038/s41416-022-02108-7 PMID: 36759720 PMC: PMC10070417
pubmed: 36759720
doi: 10.1038/s41416-022-02108-7
pii: 10.1038/s41416-022-02108-7
pmc: PMC10070417
doi:

Substances chimiques

Carboplatin BG3F62OND5
Trabectedin ID0YZQ2TCP
liposomal doxorubicin 0
Platinum 49DFR088MY
Doxorubicin 80168379AG
Polyethylene Glycols 3WJQ0SDW1A

Banques de données

ClinicalTrials.gov
['NCT01379989']

Types de publication

Randomized Controlled Trial Clinical Trial, Phase III Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1503-1513

Investigateurs

Nicoletta Colombo (N)
Angiolo Gadducci (A)
Eliana Rulli (E)
Elena Biagioli (E)
Roldano Fossati (R)
Giuseppe Funari (G)
Luciano Carlucci (L)
Davide Poli (D)
Maria Clara Caudana (MC)
Giulia Tasca (G)
Maria Ornella Nicoletto (MO)
Germana Tognon (G)
Andrea DeCensi (A)
Ugo De Giorgi (U)
Paolo Zola (P)
Dionyssios Katsaros (D)
Pierluigi Benedetti Panici (P)
Innocenza Palaia (I)
Massimo Aglietta (M)
Valentina Arcangeli (V)
Claudio Zamagni (C)
Alessandra Bologna (A)
Alessandro Bertolini (A)
Cinzia Caroti (C)
Milena Bruzzone (M)
Nicoletta Donadello (N)
Gianna Di Costanzo (G)
Alberto Zaniboni (A)
Daniela Surico (D)
Roberta Buosi (R)
Enrico Cortesi (E)
Elena Zafarana (E)
Vittorio Fusco (V)
Laura Zavallone (L)
Teresa Gamucci (T)
Filomena Narducci (F)
Valentina Musacchi (V)
Luciana Babilonti (L)
Annamaria Ferrero (A)
Luigi Cavanna (L)
Roberto Sabbatini (R)
Stefano Tamberi (S)
Maria Rosa Gentili (MR)
Grazia Artioli (G)
Antonio Ardizzoia (A)
Alessia Caldara (A)
Zuzana Sirotovà (Z)
Clelia Casartelli (C)
Michele Aieta (M)
Saverio Cinieri (S)
Elvira De Marino (E)
Stefania Gori (S)
Francesco Ferraù (F)
Livio Blasi (L)
Massimiliano Alù (M)
Sabino De Placido (S)
Carlo Milandri (C)
Cristina Churruca Galaz (C)
Maria Pilar Barretina-Ginesta (MP)
Isabel Bover (I)
Margarita Romeo (M)
Beatriz Pardo (B)
Maria Jesus Rubio-Pèrez (MJ)
Andrés Poveda (A)
Ana Santaballa (A)
Raúl Márquez (R)
Jesus Alarcon (J)
Cristina Caballero-Diaz (C)
Nuria Ruiz Miravet (N)
Eugenia Ortega (E)
Maria Angels Arcusa Lanza (MA)
Silvia Catot Tort (S)
Elena Garcia Martinez (E)
Regina Girones (R)
Yolanda Garcia (Y)
Cesar Mendiola (C)
Ana Beatriz Sanchez (AB)
Elena Garcia Martinez (E)
Jalid Sehouli (J)
Mustafa Deryal (M)
Pauline Wimberger (P)
Georg Heinrich (G)
Ingo Runnebaum (I)
Fabian Trillsch (F)
Gülten Oskay-Özcelik (G)
Maike de Wit (M)
Eva-Maria Grischke (EM)
Dirk Bauerschlag (D)
Florian Heitz (F)
Alexander Mustea (A)
Tanja Fehm (T)
Andrea Heider (A)
Max Dieterich (M)
Martina Groop-Meier (M)
Marco Battista (M)
Achim Woeckel (A)
Ivo Meinhold-Heerlein (I)
Ana Montes (A)
Rebecca Herbertson (R)
Emma Hudson (E)
Rebecca Bowen (R)
Ignace Vergote (I)
Lionel D'Hondt (L)
Peter Vuylsteke (P)
Christof Vulsteke (C)
Petronella-Beatrix Ottevanger (PB)
Anneke M Westermann (AM)
Cristiana Sessa (C)
Salome Riniker (S)
Viola Heinzelmann-Schwarz (V)
Roger Von Moos (R)
Elena Kralidis (E)
Michael Mueller (M)
Stefan Aebi (S)
Catrina Uhlmann Nussbaum (C)
Mathias Fehr (M)
Andreas Müller (A)
Christian Taverna (C)
Johanna Mäenpää (J)
Gitte-Bettina Nyvang (GB)
Mansoor Raza Mirza (MR)
Gunnar B Kristensen (GB)
Anne Gry Bentzen (AG)
Bent Fiane (B)
Ulla Puistola (U)
Maarit Anttila (M)
Christian Marth (C)
Regina Berger (R)
Edgar Petru (E)
Christian Schauer (C)
Alexander Reinthaller (A)

Informations de copyright

© 2023. The Author(s).

Références

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30.
doi: 10.3322/caac.21590 pubmed: 31912902
Wilson MK, Pujade-Lauraine E, Aoki D, Mirza MR, Lorusso D, Oza AM, et al. Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: recurrent disease. Ann Oncol. 2017;28:727–32.
doi: 10.1093/annonc/mdw663 pubmed: 27993805
Kavanagh J, Tresukosol D, Edwards C, Freedman R, Gonzalez de Leon C, Fishman A, et al. Carboplatin reinduction after taxane in patients with platinum-refractory epithelial ovarian cancer. J Clin Oncol. 1995;13:1584–8.
doi: 10.1200/JCO.1995.13.7.1584 pubmed: 7602347
Tomao F, D’Incalci M, Biagioli E, Peccatori FA, Colombo N. Restoring platinum sensitivity in recurrent ovarian cancer by extending the platinum-free interval: myth or reality? Cancer. 2017;123:3450–9.
doi: 10.1002/cncr.30830 pubmed: 28678350
Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, et al. Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol. 2010;28:3323–9.
doi: 10.1200/JCO.2009.25.7519 pubmed: 20498395
Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, et al. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol. 2010;28:3107–14.
doi: 10.1200/JCO.2009.25.4037 pubmed: 20516432
Gladieff L, Ferrero A, De Rauglaudre G, Brown C, Vasey P, Reinthaller A, et al. Carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in partially platinum-sensitive ovarian cancer patients: results from a subset analysis of the CALYPSO phase III trial. Ann Oncol. 2012;23:1185–9.
doi: 10.1093/annonc/mdr441 pubmed: 21976386
Poveda A, Vergote I, Tjulandin S, Kong B, Roy M, Chan S, et al. Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer: outcomes in the partially platinum-sensitive (platinum-free interval 6-12 months) subpopulation of OVA-301 phase III randomized trial. Ann Oncol. 2011;22:39–48.
doi: 10.1093/annonc/mdq352 pubmed: 20643862
Vergote I, Pujade-Lauraine E, Pignata S, Kristensen GB, Ledermann J, Casado A, et al. European Network of Gynaecological Oncological Trial Groups’ requirements for trials between academic groups and pharmaceutical companies. Int J Gynecol Cancer. 2010;20:476–8.
doi: 10.1111/IGC.0b013e3181d3caa8 pubmed: 20375816
Rustin GJ, Quinn M, Thigpen T, du Bois A, Pujade-Lauraine E, Jakobsen A, et al. Re: New guidelines to evaluate the response to treatment in solid tumors (ovarian cancer). J Natl Cancer Inst. 2004;96:487–8.
doi: 10.1093/jnci/djh081 pubmed: 15026475
Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–76.
doi: 10.1093/jnci/85.5.365 pubmed: 8433390
Greimel E, Bottomley A, Cull A, Waldenstrom AC, Arraras J, Chauvenet L, et al. An international field study of the reliability and validity of a disease-specific questionnaire module (the QLQ-OV28) in assessing the quality of life of patients with ovarian cancer. Eur J Cancer. 2003;39:1402–8.
doi: 10.1016/S0959-8049(03)00307-1 pubmed: 12826043
Pignata S, Scambia G, Bologna A, Signoriello S, Vergote IB, Wagner U, et al. Randomized controlled trial testing the efficacy of platinum-free interval prolongation in advanced ovarian cancer: The MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG Study. J Clin Oncol. 2017;35:3347–53.
doi: 10.1200/JCO.2017.73.4293 pubmed: 28825853
Alvarez Secord A, Berchuck A, Higgins RV, Nycum LR, Kohler MF, Puls LE, et al. A multicenter, randomized, phase 2 clinical trial to evaluate the efficacy and safety of combination docetaxel and carboplatin and sequential therapy with docetaxel then carboplatin in patients with recurrent platinum-sensitive ovarian cancer. Cancer. 2012;118:3283–93.
doi: 10.1002/cncr.26610 pubmed: 22072307
Colmegna B, Uboldi S, Frapolli R, Licandro SA, Panini N, Galmarini CM, et al. Increased sensitivity to platinum drugs of cancer cells with acquired resistance to trabectedin. Br J Cancer. 2015;113:1687–93.
doi: 10.1038/bjc.2015.407 pubmed: 26633559 pmcid: 4701998
Poveda A, Ray-Coquard I, Romero I, Lopez-Guerrero JA, Colombo N. Emerging treatment strategies in recurrent platinum-sensitive ovarian cancer: focus on trabectedin. Cancer Treat Rev. 2014;40:366–75.
doi: 10.1016/j.ctrv.2013.08.001 pubmed: 24296108
Lorusso D, Scambia G, Pignata S, Sorio R, Amadio G, Lepori S, et al. Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients: the MITO 15 trial. Ann Oncol. 2016;27:487–93.
doi: 10.1093/annonc/mdv608 pubmed: 26681678
Pignata S, Scambia G, Villanucci A, Naglieri E, Ibarbia MA, Brusa F, et al. A European, observational, prospective trial of trabectedin plus pegylated liposomal doxorubicin in patients with platinum-sensitive ovarian cancer. Oncologist. 2021;26:e658–e68.
doi: 10.1002/onco.13630 pubmed: 33289956 pmcid: 8018301
Monk BJ, Herzog TJ, Wang G, Triantos S, Maul S, Knoblauch R, et al. A phase 3 randomized, open-label, multicenter trial for safety and efficacy of combined trabectedin and pegylated liposomal doxorubicin therapy for recurrent ovarian cancer. Gynecol Oncol. 2020;156:535–44.
doi: 10.1016/j.ygyno.2019.12.043 pubmed: 31924332
Erba E, Bergamaschi D, Bassano L, Damia G, Ronzoni S, Faircloth GT, et al. Ecteinascidin-743 (ET-743), a natural marine compound, with a unique mechanism of action. Eur J Cancer. 2001;37:97–105.
doi: 10.1016/S0959-8049(00)00357-9 pubmed: 11165136
Damia G, Silvestri S, Carrassa L, Filiberti L, Faircloth GT, Liberi G, et al. Unique pattern of ET-743 activity in different cellular systems with defined deficiencies in DNA-repair pathways. Int J Cancer. 2001;92:583–8.
doi: 10.1002/ijc.1221 pubmed: 11304695
Monk BJ, Ghatage P, Parekh T, Henitz E, Knoblauch R, Matos-Pita AS, et al. Effect of BRCA1 and XPG mutations on treatment response to trabectedin and pegylated liposomal doxorubicin in patients with advanced ovarian cancer: exploratory analysis of the phase 3 OVA-301 study. Ann Oncol. 2015;26:914–20.
doi: 10.1093/annonc/mdv071 pubmed: 25722380
Scambia G, Raspagliesi F, Valabrega G, Colombo N, Pisano C, Cassani C, et al. Randomized phase III trial on trabectedin (ET-743) single agent versus clinician’s choice chemotherapy in recurrent ovarian, primary peritoneal, or fallopian tube cancers of BRCA-mutated or BRCAness phenotype patients (MITO23). J Clin Oncol. 2022;40:LBA5504–LBA.
doi: 10.1200/JCO.2022.40.17_suppl.LBA5504
Frenel JS, Kim JW, Berton-Rigaud D, Asher R, Vidal L, Pautier P, et al. Efficacy of subsequent chemotherapy for patients with BRCA1/2 mutated platinum-sensitive recurrent epithelial ovarian cancer (EOC) progressing on olaparib vs placebo: The SOLO2/ENGOT Ov-21 trial. Ann Oncol. 2020;31:S615.
doi: 10.1016/j.annonc.2020.08.952
Colombo N, Zaccarelli E, Baldoni A, Frezzini S, Scambia G, Palluzzi E, et al. Multicenter, randomised, open-label, non-comparative phase 2 trial on the efficacy and safety of the combination of bevacizumab and trabectedin with or without carboplatin in women with partially platinum-sensitive recurrent ovarian cancer. Br J Cancer. 2019;121:744–50.
doi: 10.1038/s41416-019-0584-5 pubmed: 31537908 pmcid: 6888836

Auteurs

N Colombo (N)

Gynecologic Cancer Program, European Institute of Oncology IRCCS and University of Milan-Bicocca, Milan, Italy.

A Gadducci (A)

Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy.

J Sehouli (J)

North Eastern German Society of Gynecological Oncology (NOGGO) Study group and Gynecology with Center for Oncological Surgery, European Competence Center for Ovarian Cancer, Charité-Berlin University of Medicine, Berlin, Germany.

E Rulli (E)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

J Mäenpää (J)

Nordic Society of Gynecologic Oncology Clinical Trial Unit (NSGO-CTU) & Department of Obstetrics and Gynaecology and Tays Cancer Centre Tampere University and University Hospital, Tampere, Finland.

C Sessa (C)

Istituto Oncologico della Svizzera Italiana, IOSI and Swiss Group for Clinical Cancer Research (SAKK), Bellinzona, Switzerland.

A Montes (A)

Guys and St Thomas' NHS Foundation Trust, London, UK.

N B Ottevanger (NB)

Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands.
ORCID: 0000-0001-8209-487X

R Berger (R)

Medical University of Innsbruck, Department for Gynecology and Obstetrics, Innsbruck, Austria, and AGO, Innsbruck, Austria.

I Vergote (I)

Gynecologic Oncology, University Hospitals Leuven, Leuven Cancer Institute, and Belgian Gynaecological Oncology Group (BGOG), European Union, Leuven, Belgium.

M D'Incalci (M)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
ORCID: 0000-0001-8784-1360

C Churruca Galaz (C)

Hospital de Donosti San Sebastián and Grupo Español de Cáncer de Ovario (GEICO), de Donosti San, Spain.

R Chekerov (R)

North Eastern German Society of Gynecological Oncology (NOGGO) Study group and Gynecology with Center for Oncological Surgery, European Competence Center for Ovarian Cancer, Charité-Berlin University of Medicine, Berlin, Germany.

G B Nyvang (GB)

Nordic Society of Gynecologic Oncology Clinical Trial Unit (NSGO-CTU) & Department of Oncology, Odense University Hospital, Odense, Denmark.

S Riniker (S)

Oncology, Kantonsspital St. Gallen and Swiss Group for Clinical Cancer Research (SAKK), St. Gallen, Switzerland.

R Herbertson (R)

Brighton and Sussex University Hospitals NHS Trust, Brighton, UK.

R Fossati (R)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

M P Barretina-Ginesta (MP)

Institut Catalá de Oncología de Girona and Grupo Español de Cáncer de Ovario (GEICO), de Donosti San, Spain.

M Deryal (M)

North Eastern German Society of Gynecological Oncology (NOGGO) Study group and CaritasKlinikum St. Theresia-Saarbruecken, Saarbruecken, Germany.

M R Mirza (MR)

Nordic Society of Gynecologic Oncology Clinical Trial Unit (NSGO-CTU) & Department of Cancer Treatment, Copenhagen University Hospital, Copenhagen, Denmark.

E Biagioli (E)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. elena.biagioli@marionegri.it.
ORCID: 0000-0002-2066-3827

M Iglesias (M)

Hospital Son Llázter and Grupo Español de Cáncer de Ovario (GEICO), Palma, Spain.

G Funari (G)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

M Romeo (M)

Institut Catalá de Oncología de Badalona and Grupo Español de Cáncer de Ovario (GEICO), de Donosti San, Spain.

G Tasca (G)

Oncologia 2, Istituto Oncologico Veneto, Padua, Italy.

B Pardo (B)

Institut Catalá de Oncología de Hospitalet and Grupo Español de Cáncer de Ovario (GEICO), Barcelona, Spain.

G Tognon (G)

Obstetrics and Gynaecology, ASST Spedali Civili-Università degli Studi di Brescia, Brescia, Italy.

M J Rubio-Pérez (MJ)

Hospital Reina Sofía Córdoba and Grupo Español de Cáncer de Ovario (GEICO), de Donosti San, Spain.

A DeCensi (A)

S.C. Oncologia Medica, E.O. Ospedali Galliera, Genoa, Italy.

U De Giorgi (U)

IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
ORCID: 0000-0001-7520-2908

P Zola (P)

AOU Città della Salute e della Scienza - OIRM S. Anna, Torino, Italy.

P Benedetti Panici (P)

AOU Policlinico Umberto I di Roma, Rome, Italy.

M Aglietta (M)

Istituto di Candiolo, FPO-IRCCS and University of Torino, Torino, Italy.

V Arcangeli (V)

Ospedale Infermi, Rimini, Italy.

C Zamagni (C)

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

A Bologna (A)

Azienda Unità Sanitaria Locale di Reggio Emilia IRCCS, Reggio Emilia, Italy.

A Westermann (A)

Amsterdam UMC, Amsterdam, Netherlands.

V Heinzelmann-Schwarz (V)

Universitätsspital Basel, USB andSwiss Group for Clinical Cancer Research (SAKK), Basel, Switzerland.

I Tsibulak (I)

Medical University of Innsbruck, Department for Gynecology and Obstetrics, Innsbruck, Austria, and AGO, Innsbruck, Austria.

P Wimberger (P)

North Eastern German Society of Gynecological Oncology (NOGGO) Study group and Department of Gynecology and Obstetrics, Technische Universität Dresden, Fetscherstr, Dresden, Germany.
National Center for Tumor Diseases (NCT/UCC), Dresden, Germany.
German Cancer Research Center (DKFZ), Heidelberg, Germany.
Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.

A Poveda (A)

Initia Oncologia and Grupo Español de Cáncer de Ovario (GEICO), Valencia, Spain.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › INOVATYON/ ENGOT-ov5 study: Randomized phase...
Recherchemedicale.com › Composés chimiques organiques › Complexes de coordination › Carboplatine › INOVATYON/ ENGOT-ov5 study: Randomized phase...
Recherchemedicale.com › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Isoquinoléines › Tétrahydroisoquinoléines › Trabectédine › INOVATYON/ ENGOT-ov5 study: Randomized phase...
Recherchemedicale.com › Maladies endocriniennes › Troubles gonadiques › Maladies ovariennes › Tumeurs de l'ovaire › INOVATYON/ ENGOT-ov5 study: Randomized phase...
Recherchemedicale.com › Produits chimiques inorganiques › Métaux › Métaux lourds › Platine › INOVATYON/ ENGOT-ov5 study: Randomized phase...
Recherchemedicale.com › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Récidive tumorale locale › INOVATYON/ ENGOT-ov5 study: Randomized phase...
Recherchemedicale.com › Maladies endocriniennes › Troubles gonadiques › Maladies ovariennes › Tumeurs de l'ovaire › Carcinome épithélial de l'ovaire › INOVATYON/ ENGOT-ov5 study: Randomized phase...
Recherchemedicale.com › Glucides › Hétérosides › Aminosides › Anthracyclines › Daunorubicine › Doxorubicine › INOVATYON/ ENGOT-ov5 study: Randomized phase...
Recherchemedicale.com › Technologie, industrie et agriculture › Produits manufacturés › Matériaux biomédicaux et dentaires › Polymères › Polyéthylène glycols › INOVATYON/ ENGOT-ov5 study: Randomized phase...
Recherchemedicale.com › Thérapeutique › Traitement médicamenteux › Association de médicaments › Protocoles de polychimiothérapie antinéoplasique › INOVATYON/ ENGOT-ov5 study: Randomized phase...