{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T06:54:39Z","timestamp":1770965679129,"version":"3.50.1"},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[1997,1]]},"abstract":"PURPOSE<\/jats:title> To evaluate the biologic interactions and toxicities of melphalan (L-PAM) combined with 41.8 degrees C whole-body hyperthermia (WBH) for 60 minutes. <\/jats:p><\/jats:sec>PATIENTS AND METHODS<\/jats:title> Sixteen patients with refractory cancer were treated (May 1992 to May 1995) with WBH alone during week 1) thereafter patients were randomized to receive either L-PAM alone on week 2 and L-PAM plus WBH on week 5, or the reverse sequence. Patients who demonstrated clinical improvement received WBH plus L-PAM monthly. Dose levels of L-PAM were 10 mg\/m2 (n = 3), 15 mg\/m2 (n = 3), 17.5 mg\/m2 (n = 6), and 20 mg\/m2 (n = 4). L-PAM was administered at target temperature; WBH was administered with an Aquatherm radiant-heat device (patent pending; Cancer Research Institute, New York, NY). <\/jats:p><\/jats:sec>RESULTS<\/jats:title> Comparisons of mean WBC count and platelet nadirs for L-PAM alone and L-PAM plus WBH demonstrated that the addition of WBH resulted in nadir counts that were, on average, 25% lower. There were no instances of febrile neutropenia or bleeding. Toxicities allowed for escalation of L-PAM to 20 mg\/m2; all four patients at this level experienced grade 4 myelosuppression. No significant myelosuppression was observed at 10 and 15 mg\/m2. Grade 3 myelosuppression was observed in two of six patients at 17.5 mg\/m2. Responses included complete remission (CR) of pancreatic cancer (10 mg\/m2), partial remission (PR) of malignant melanoma in two patients (20 mg\/m2), and transient clinical and\/or serologic improvement in five patients. The pharmacokinetics of L-PAM were not altered by WBH. Observed cytokine induction by WBH is also discussed in detail. <\/jats:p><\/jats:sec>CONCLUSION<\/jats:title> We conclude that L-PAM with 41.8 degrees C WBH is well tolerated. Clinical results are consistent with preclinical predictions and provide a foundation for second-generation trials now in progress. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.1997.15.1.158","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T09:51:47Z","timestamp":1487929907000},"page":"158-164","source":"Crossref","is-referenced-by-count":39,"title":["Phase I clinical trial of melphalan and 41.8 degrees C whole-body hyperthermia in cancer patients."],"prefix":"10.1200","volume":"15","author":[{"given":"H I","family":"Robins","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Rushing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Kutz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K D","family":"Tutsch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C L","family":"Tiggelaar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Paul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Spriggs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Kraemer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Gillis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Feierabend","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R Z","family":"Arzoomanian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Longo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Alberti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"d'Oleire","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R P","family":"Qu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Wilding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J A","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.1997.15.1.158","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T22:09:27Z","timestamp":1653516567000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.1997.15.1.158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1997,1]]}},"alternative-id":["10.1200\/JCO.1997.15.1.158"],"URL":"https:\/\/doi.org\/10.1200\/jco.1997.15.1.158","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,1]]}}}