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

H. I. Robins, D. Rushing, M. Kutz, K. D. Tutsch, C. L. Tiggelaar, D. Paul, D. Spriggs, C. Kraemer, W. Gillis, C. Feierabend, R. Z. Arzoomanian, W. Longo, D. Alberti, F. d'Oleire, R. P. Qu, G. Wilding, J. A. Stewart

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Abstract

Purpose: To evaluate the biologic interactions and toxicities of melphalan (L-PAM) combined with 41.8°C whole-body hyperthermia (WBH) for 60 minutes. Patients and Methods: 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). Results: Comparisons of mean WBC count and platelet nadirs far 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 in stances 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. Conclusion: We conclude that L-PAM with 41.8°C WBH is well tolerated. Clinical results are consistent with preclinical predictions and provide a foundation for second-generation trials now in progress.

Original languageEnglish (US)
Pages (from-to)158-164
Number of pages7
JournalJournal of Clinical Oncology
Volume15
Issue number1
StatePublished - Jan 1997
Externally publishedYes

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Clinical Trials, Phase I
Melphalan
Fever
Neoplasms
Febrile Neutropenia
Platelet Count
Pancreatic Neoplasms
Melanoma
Pharmacokinetics
Hot Temperature

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Robins, H. I., Rushing, D., Kutz, M., Tutsch, K. D., Tiggelaar, C. L., Paul, D., ... Stewart, J. A. (1997). Phase I clinical trial of melphalan and 41.8°C whole-body hyperthermia in cancer patients. Journal of Clinical Oncology, 15(1), 158-164.

Phase I clinical trial of melphalan and 41.8°C whole-body hyperthermia in cancer patients. / Robins, H. I.; Rushing, D.; Kutz, M.; Tutsch, K. D.; Tiggelaar, C. L.; Paul, D.; Spriggs, D.; Kraemer, C.; Gillis, W.; Feierabend, C.; Arzoomanian, R. Z.; Longo, W.; Alberti, D.; d'Oleire, F.; Qu, R. P.; Wilding, G.; Stewart, J. A.

In: Journal of Clinical Oncology, Vol. 15, No. 1, 01.1997, p. 158-164.

Research output: Contribution to journalArticle

Robins, HI, Rushing, D, Kutz, M, Tutsch, KD, Tiggelaar, CL, Paul, D, Spriggs, D, Kraemer, C, Gillis, W, Feierabend, C, Arzoomanian, RZ, Longo, W, Alberti, D, d'Oleire, F, Qu, RP, Wilding, G & Stewart, JA 1997, 'Phase I clinical trial of melphalan and 41.8°C whole-body hyperthermia in cancer patients', Journal of Clinical Oncology, vol. 15, no. 1, pp. 158-164.
Robins HI, Rushing D, Kutz M, Tutsch KD, Tiggelaar CL, Paul D et al. Phase I clinical trial of melphalan and 41.8°C whole-body hyperthermia in cancer patients. Journal of Clinical Oncology. 1997 Jan;15(1):158-164.
Robins, H. I. ; Rushing, D. ; Kutz, M. ; Tutsch, K. D. ; Tiggelaar, C. L. ; Paul, D. ; Spriggs, D. ; Kraemer, C. ; Gillis, W. ; Feierabend, C. ; Arzoomanian, R. Z. ; Longo, W. ; Alberti, D. ; d'Oleire, F. ; Qu, R. P. ; Wilding, G. ; Stewart, J. A. / Phase I clinical trial of melphalan and 41.8°C whole-body hyperthermia in cancer patients. In: Journal of Clinical Oncology. 1997 ; Vol. 15, No. 1. pp. 158-164.
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abstract = "Purpose: To evaluate the biologic interactions and toxicities of melphalan (L-PAM) combined with 41.8°C whole-body hyperthermia (WBH) for 60 minutes. Patients and Methods: 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). Results: Comparisons of mean WBC count and platelet nadirs far 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 in stances 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. Conclusion: We conclude that L-PAM with 41.8°C WBH is well tolerated. Clinical results are consistent with preclinical predictions and provide a foundation for second-generation trials now in progress.",
author = "Robins, {H. I.} and D. Rushing and M. Kutz and Tutsch, {K. D.} and Tiggelaar, {C. L.} and D. Paul and D. Spriggs and C. Kraemer and W. Gillis and C. Feierabend and Arzoomanian, {R. Z.} and W. Longo and D. Alberti and F. d'Oleire and Qu, {R. P.} and G. Wilding and Stewart, {J. A.}",
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T1 - Phase I clinical trial of melphalan and 41.8°C whole-body hyperthermia in cancer patients

AU - Robins, H. I.

AU - Rushing, D.

AU - Kutz, M.

AU - Tutsch, K. D.

AU - Tiggelaar, C. L.

AU - Paul, D.

AU - Spriggs, D.

AU - Kraemer, C.

AU - Gillis, W.

AU - Feierabend, C.

AU - Arzoomanian, R. Z.

AU - Longo, W.

AU - Alberti, D.

AU - d'Oleire, F.

AU - Qu, R. P.

AU - Wilding, G.

AU - Stewart, J. A.

PY - 1997/1

Y1 - 1997/1

N2 - Purpose: To evaluate the biologic interactions and toxicities of melphalan (L-PAM) combined with 41.8°C whole-body hyperthermia (WBH) for 60 minutes. Patients and Methods: 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). Results: Comparisons of mean WBC count and platelet nadirs far 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 in stances 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. Conclusion: We conclude that L-PAM with 41.8°C WBH is well tolerated. Clinical results are consistent with preclinical predictions and provide a foundation for second-generation trials now in progress.

AB - Purpose: To evaluate the biologic interactions and toxicities of melphalan (L-PAM) combined with 41.8°C whole-body hyperthermia (WBH) for 60 minutes. Patients and Methods: 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). Results: Comparisons of mean WBC count and platelet nadirs far 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 in stances 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. Conclusion: We conclude that L-PAM with 41.8°C WBH is well tolerated. Clinical results are consistent with preclinical predictions and provide a foundation for second-generation trials now in progress.

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