{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T13:40:05Z","timestamp":1777642805527,"version":"3.51.4"},"reference-count":17,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"17","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2022,6,10]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p>Cancer drug development has largely shifted from cytotoxic chemotherapy to targeted treatment in the past two decades. Although previous studies have highlighted improvement in response rates in recent phase I trials, disease-focused reporting is limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We integrated patient-level data for patients with hematologic malignancies who participated in phase I trials sponsored by the National Cancer Institute Cancer Therapy Evaluation Program between January 2000 and May 2019 and estimated the trend of grade 5 toxicity and response by disease subtype over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>We analyzed 161 trials involving 3,308 patients, all of whom were assessed for toxicity and 2,404 of whom were evaluable for response to therapy. The overall rate of grade 5 toxicities was 1.81% (95% CI, 1.36 to 2.27), with no significant change in the rate over time. Baseline characteristics associated with higher risk of grade 5 toxicity were age and performance status \u2265 2 at enrollment. Overall response rate (ORR) and complete response (CR) rate for all trials during the study period were 25.1% and 14.7%, respectively. A significant increase in both ORR and CR rate was observed over time (ORR, 18.5% in 2000-2005, 25.9% in 2006-2012, and 50.6% in 2013-2019, P &lt; .001). ORR in phase I trials varied across disease subtypes: 20.2% in acute myeloid leukemia, 9.1% in myelodysplastic syndrome, 43.2% in lymphoma, 42.9% in chronic lymphocytic leukemia, 15.1% in acute lymphoblastic leukemia, and 16.5% in myeloma.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Over time, the ORR and CR rates in phase I trials for hematologic malignancy have improved meaningfully, whereas the rate of toxicity-related death remains stable. This study provides broad experience that physicians can use when discussing the potential outcomes for patients with hematologic malignancy considering participation in phase I trials.<\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.21.02190","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T20:59:17Z","timestamp":1646859557000},"page":"1949-1957","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":11,"title":["Trends in Grade 5 Toxicity and Response in Phase I Trials in Hematologic Malignancy: 20-Year Experience From the Cancer Therapy Evaluation Program at the National Cancer Institute"],"prefix":"10.1200","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1153-2294","authenticated-orcid":false,"given":"Dai","family":"Chihara","sequence":"first","affiliation":[{"name":"Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX"},{"name":"Medical Oncology Service, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erich P.","family":"Huang","sequence":"additional","affiliation":[{"name":"Biometric Research Program, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0555-8965","authenticated-orcid":false,"given":"Shanda R.","family":"Finnigan","sequence":"additional","affiliation":[{"name":"Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3833-4084","authenticated-orcid":false,"given":"Lisa M.","family":"Cordes","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0854-3360","authenticated-orcid":false,"given":"Nebojsa","family":"Skorupan","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4340-5492","authenticated-orcid":false,"given":"Yoko","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9720-9737","authenticated-orcid":false,"given":"Larry V.","family":"Rubinstein","sequence":"additional","affiliation":[{"name":"Biometric Research Program, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7747-072X","authenticated-orcid":false,"given":"S. Percy","family":"Ivy","sequence":"additional","affiliation":[{"name":"Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James H.","family":"Doroshow","sequence":"additional","affiliation":[{"name":"Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loretta J.","family":"Nastoupil","sequence":"additional","affiliation":[{"name":"Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9524-3990","authenticated-orcid":false,"given":"Christopher R.","family":"Flowers","sequence":"additional","affiliation":[{"name":"Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5790-4954","authenticated-orcid":false,"given":"Naoko","family":"Takebe","sequence":"additional","affiliation":[{"name":"Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"b1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.9902"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsa042220"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.17.2130"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1007\/BF00194562"},{"key":"b5","first-page":"1105","volume":"70","author":"Estey E","year":"1986","journal-title":"Cancer Treat Rep"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0311-4"},{"key":"b7","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.58.2635"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1803837"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.2129"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609324"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011795"},{"key":"b12","doi-asserted-by":"publisher","DOI":"10.1016\/j.hpopen.2020.100015"},{"key":"b14","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Benjamini Y","year":"1995","journal-title":"J R Stat Soc Ser B"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0262-9"},{"key":"b16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2020.04.037"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv335"},{"key":"b18","volume-title":"List of Agents Available Under CTEP Collaborative Agreements for Clinical and Non-clinical Studies","year":"2021"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.21.02190","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:29:52Z","timestamp":1726792192000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.21.02190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,10]]},"references-count":17,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2022,6,10]]}},"alternative-id":["10.1200\/JCO.21.02190"],"URL":"https:\/\/doi.org\/10.1200\/jco.21.02190","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,10]]},"assertion":[{"value":"2021-09-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-05","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}