Phase I clinical trial of carboplatin and 41.8°C whole-body hyperthermia in cancer patients

H. Ian Robins, Justin D. Cohen, Cynthia L. Schmitt, Kendra D. Tutsch, Chris Feierabend, Rhoda Z. Arzoomanian, Dona Alberti, Floriane D'Oleire, Walter Longo, Cathy Heiss, Daniel Rushing, Richard Love, David Spriggs

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Purpose: To evaluate the biologic interactions and toxicities of carboplatin combined with 41.8°C wholebody hyperthermia (WBH) for 60 minutes in a phase I clinical trial. Patients and Methods: Thirty assessable patients with cancer refractory to conventional therapy were treated. During induction therapy, patients received WBH alone in week 1, WBH plus carboplatin in week 2, and carboplatin alone in week 5. Carboplatin dose was escalated (three patients per group) as follows: 100, 150, 200, 250, 300, 350, 400, 480, and 575 mg/m2; three additional patients were entered at 480 mg/m3. Carboplatin was administered at target temperature. Results: Comparisons of the mean/median WBC and platelet nadirs for carboplatin alone and carboplatin plus WBH demonstrated no enhancing effect by WBH. Toxicities including nausea and/or vomiting, as well as myelosuppression, were within acceptable limits, allowing for escalation to a dose of 575 mg/m2; three of three patients at this dose level experienced grade 4 myelosuppression with no associated infection or bleeding. No renal toxicity was observed. Analysis of platinum in plasma ultrafiltrate and urine showed only slight effects of WBH on the pharmacokinetics and renal excretion of platinum. Responses included the following: lung - minor response (200 mg/m2); gastrointestinal neuroendocrine - complete response (CR) (400 mg/m2); pancreatic - partial response (PR) (480 mg/m2); small bowel - PR (575 mg/m2); ovarian - CR, two patients (575 mg/m3), with marker data suggesting WBH enhancement of carboplatin cytotoxicity. Another three patients experienced clinical improvement after WBH plus carboplatin, but progression with carboplatin alone (lung, 400 mg/m2; gastrointestinal neuroendocrine, 480 mg/m2; melanoma, 480 mg/m2). Conclusion: We conclude that carboplatin with WBH is well tolerated even at conventional carboplatin doses. Clinical results are consistent with preclinical predictions of an increased therapeutic index for this combination, which encourages future clinical studies.

Original languageEnglish (US)
Pages (from-to)1787-1794
Number of pages8
JournalJournal of Clinical Oncology
Volume11
Issue number9
StatePublished - 1993
Externally publishedYes

Fingerprint

Clinical Trials, Phase I
Carboplatin
Fever
Neoplasms
Platinum
Lung
Nausea
Vomiting
Melanoma
Therapeutics
Blood Platelets
Pharmacokinetics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ian Robins, H., Cohen, J. D., Schmitt, C. L., Tutsch, K. D., Feierabend, C., Arzoomanian, R. Z., ... Spriggs, D. (1993). Phase I clinical trial of carboplatin and 41.8°C whole-body hyperthermia in cancer patients. Journal of Clinical Oncology, 11(9), 1787-1794.

Phase I clinical trial of carboplatin and 41.8°C whole-body hyperthermia in cancer patients. / Ian Robins, H.; Cohen, Justin D.; Schmitt, Cynthia L.; Tutsch, Kendra D.; Feierabend, Chris; Arzoomanian, Rhoda Z.; Alberti, Dona; D'Oleire, Floriane; Longo, Walter; Heiss, Cathy; Rushing, Daniel; Love, Richard; Spriggs, David.

In: Journal of Clinical Oncology, Vol. 11, No. 9, 1993, p. 1787-1794.

Research output: Contribution to journalArticle

Ian Robins, H, Cohen, JD, Schmitt, CL, Tutsch, KD, Feierabend, C, Arzoomanian, RZ, Alberti, D, D'Oleire, F, Longo, W, Heiss, C, Rushing, D, Love, R & Spriggs, D 1993, 'Phase I clinical trial of carboplatin and 41.8°C whole-body hyperthermia in cancer patients', Journal of Clinical Oncology, vol. 11, no. 9, pp. 1787-1794.
Ian Robins H, Cohen JD, Schmitt CL, Tutsch KD, Feierabend C, Arzoomanian RZ et al. Phase I clinical trial of carboplatin and 41.8°C whole-body hyperthermia in cancer patients. Journal of Clinical Oncology. 1993;11(9):1787-1794.
Ian Robins, H. ; Cohen, Justin D. ; Schmitt, Cynthia L. ; Tutsch, Kendra D. ; Feierabend, Chris ; Arzoomanian, Rhoda Z. ; Alberti, Dona ; D'Oleire, Floriane ; Longo, Walter ; Heiss, Cathy ; Rushing, Daniel ; Love, Richard ; Spriggs, David. / Phase I clinical trial of carboplatin and 41.8°C whole-body hyperthermia in cancer patients. In: Journal of Clinical Oncology. 1993 ; Vol. 11, No. 9. pp. 1787-1794.
@article{dc71e513e5054ac3818022e8e9c82144,
title = "Phase I clinical trial of carboplatin and 41.8°C whole-body hyperthermia in cancer patients",
abstract = "Purpose: To evaluate the biologic interactions and toxicities of carboplatin combined with 41.8°C wholebody hyperthermia (WBH) for 60 minutes in a phase I clinical trial. Patients and Methods: Thirty assessable patients with cancer refractory to conventional therapy were treated. During induction therapy, patients received WBH alone in week 1, WBH plus carboplatin in week 2, and carboplatin alone in week 5. Carboplatin dose was escalated (three patients per group) as follows: 100, 150, 200, 250, 300, 350, 400, 480, and 575 mg/m2; three additional patients were entered at 480 mg/m3. Carboplatin was administered at target temperature. Results: Comparisons of the mean/median WBC and platelet nadirs for carboplatin alone and carboplatin plus WBH demonstrated no enhancing effect by WBH. Toxicities including nausea and/or vomiting, as well as myelosuppression, were within acceptable limits, allowing for escalation to a dose of 575 mg/m2; three of three patients at this dose level experienced grade 4 myelosuppression with no associated infection or bleeding. No renal toxicity was observed. Analysis of platinum in plasma ultrafiltrate and urine showed only slight effects of WBH on the pharmacokinetics and renal excretion of platinum. Responses included the following: lung - minor response (200 mg/m2); gastrointestinal neuroendocrine - complete response (CR) (400 mg/m2); pancreatic - partial response (PR) (480 mg/m2); small bowel - PR (575 mg/m2); ovarian - CR, two patients (575 mg/m3), with marker data suggesting WBH enhancement of carboplatin cytotoxicity. Another three patients experienced clinical improvement after WBH plus carboplatin, but progression with carboplatin alone (lung, 400 mg/m2; gastrointestinal neuroendocrine, 480 mg/m2; melanoma, 480 mg/m2). Conclusion: We conclude that carboplatin with WBH is well tolerated even at conventional carboplatin doses. Clinical results are consistent with preclinical predictions of an increased therapeutic index for this combination, which encourages future clinical studies.",
author = "{Ian Robins}, H. and Cohen, {Justin D.} and Schmitt, {Cynthia L.} and Tutsch, {Kendra D.} and Chris Feierabend and Arzoomanian, {Rhoda Z.} and Dona Alberti and Floriane D'Oleire and Walter Longo and Cathy Heiss and Daniel Rushing and Richard Love and David Spriggs",
year = "1993",
language = "English (US)",
volume = "11",
pages = "1787--1794",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "9",

}

TY - JOUR

T1 - Phase I clinical trial of carboplatin and 41.8°C whole-body hyperthermia in cancer patients

AU - Ian Robins, H.

AU - Cohen, Justin D.

AU - Schmitt, Cynthia L.

AU - Tutsch, Kendra D.

AU - Feierabend, Chris

AU - Arzoomanian, Rhoda Z.

AU - Alberti, Dona

AU - D'Oleire, Floriane

AU - Longo, Walter

AU - Heiss, Cathy

AU - Rushing, Daniel

AU - Love, Richard

AU - Spriggs, David

PY - 1993

Y1 - 1993

N2 - Purpose: To evaluate the biologic interactions and toxicities of carboplatin combined with 41.8°C wholebody hyperthermia (WBH) for 60 minutes in a phase I clinical trial. Patients and Methods: Thirty assessable patients with cancer refractory to conventional therapy were treated. During induction therapy, patients received WBH alone in week 1, WBH plus carboplatin in week 2, and carboplatin alone in week 5. Carboplatin dose was escalated (three patients per group) as follows: 100, 150, 200, 250, 300, 350, 400, 480, and 575 mg/m2; three additional patients were entered at 480 mg/m3. Carboplatin was administered at target temperature. Results: Comparisons of the mean/median WBC and platelet nadirs for carboplatin alone and carboplatin plus WBH demonstrated no enhancing effect by WBH. Toxicities including nausea and/or vomiting, as well as myelosuppression, were within acceptable limits, allowing for escalation to a dose of 575 mg/m2; three of three patients at this dose level experienced grade 4 myelosuppression with no associated infection or bleeding. No renal toxicity was observed. Analysis of platinum in plasma ultrafiltrate and urine showed only slight effects of WBH on the pharmacokinetics and renal excretion of platinum. Responses included the following: lung - minor response (200 mg/m2); gastrointestinal neuroendocrine - complete response (CR) (400 mg/m2); pancreatic - partial response (PR) (480 mg/m2); small bowel - PR (575 mg/m2); ovarian - CR, two patients (575 mg/m3), with marker data suggesting WBH enhancement of carboplatin cytotoxicity. Another three patients experienced clinical improvement after WBH plus carboplatin, but progression with carboplatin alone (lung, 400 mg/m2; gastrointestinal neuroendocrine, 480 mg/m2; melanoma, 480 mg/m2). Conclusion: We conclude that carboplatin with WBH is well tolerated even at conventional carboplatin doses. Clinical results are consistent with preclinical predictions of an increased therapeutic index for this combination, which encourages future clinical studies.

AB - Purpose: To evaluate the biologic interactions and toxicities of carboplatin combined with 41.8°C wholebody hyperthermia (WBH) for 60 minutes in a phase I clinical trial. Patients and Methods: Thirty assessable patients with cancer refractory to conventional therapy were treated. During induction therapy, patients received WBH alone in week 1, WBH plus carboplatin in week 2, and carboplatin alone in week 5. Carboplatin dose was escalated (three patients per group) as follows: 100, 150, 200, 250, 300, 350, 400, 480, and 575 mg/m2; three additional patients were entered at 480 mg/m3. Carboplatin was administered at target temperature. Results: Comparisons of the mean/median WBC and platelet nadirs for carboplatin alone and carboplatin plus WBH demonstrated no enhancing effect by WBH. Toxicities including nausea and/or vomiting, as well as myelosuppression, were within acceptable limits, allowing for escalation to a dose of 575 mg/m2; three of three patients at this dose level experienced grade 4 myelosuppression with no associated infection or bleeding. No renal toxicity was observed. Analysis of platinum in plasma ultrafiltrate and urine showed only slight effects of WBH on the pharmacokinetics and renal excretion of platinum. Responses included the following: lung - minor response (200 mg/m2); gastrointestinal neuroendocrine - complete response (CR) (400 mg/m2); pancreatic - partial response (PR) (480 mg/m2); small bowel - PR (575 mg/m2); ovarian - CR, two patients (575 mg/m3), with marker data suggesting WBH enhancement of carboplatin cytotoxicity. Another three patients experienced clinical improvement after WBH plus carboplatin, but progression with carboplatin alone (lung, 400 mg/m2; gastrointestinal neuroendocrine, 480 mg/m2; melanoma, 480 mg/m2). Conclusion: We conclude that carboplatin with WBH is well tolerated even at conventional carboplatin doses. Clinical results are consistent with preclinical predictions of an increased therapeutic index for this combination, which encourages future clinical studies.

UR - http://www.scopus.com/inward/record.url?scp=0027171586&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027171586&partnerID=8YFLogxK

M3 - Article

C2 - 8355046

AN - SCOPUS:0027171586

VL - 11

SP - 1787

EP - 1794

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 9

ER -