A pilot study of melphalan, tumor necrosis factor-α and 41.8 °C whole- body hyperthermia

H. I. Robins, D. M. Katschinski, W. Longo, E. Grosen, G. Wilding, W. Gillis, C. Kraemer, C. L. Tiggelaar, D. Rushing, J. A. Stewart, D. Spriggs, R. Love, R. Z. Arzoomanian, C. Feierabend, D. Alberti, K. Morgan, K. Simon, F. D'Oleire

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Purpose: To evaluate the feasibility of sequencing (based on preclinical modeling) tumor necrosis factor-α (TNF) at two dose levels with melphalan (L-PAM) and 41.8 °C whole-body hyperthermia (WBH) for 60 min. Patients and methods: Nine patients with refractory cancer were treated from October 1995 to June 1997. The study encompassed a total of 20 trimodality treatment courses. Three patients were treated at TNF dose level I (50 μg/m2) and six patients were treated at TNF dose level II (100 μg/m2). TNF was delivered as a 24-h intravenous infusion, 48 h prior to the combination of L-PAM and WBH; L-PAM was given over 10 min at target temperature at a dose of 17.5 mg/m2 based on a previous phase I WBH/L-PAM trial. WBH was administered with an Aquatherm radiant heat device. Results: Myelosuppression was the major toxicity associated with therapy, but there were no instances of bleeding or neutropenic fevers. Grade 3 thrombocytopenia was seen with 15% of treatments. Regarding absolute neutrophil count, 15% of treatments were associated with grade 3 toxicity, and 45% with grade 4 toxicity, and regarding white blood cell count, 50% of treatments were associated with grade 3 toxicity and 10% with grade 4 toxicity. The myelosuppression observed was equivalent to that seen in our earlier phase I study of WBH and L-PAM (without TNF). Only mild toxicities (grade 1 or 2) were associated with TNF; these were seen with ≤25% of treatments and included nausea, vomiting, diarrhea, fevers, and headache. There were no instances of hypotension. There was no relationship between toxicities observed and the two TNF dose levels. Mild WBH toxicities were seen with less than 15% of treatments; these included nausea, vomiting, and herpes simplex I. Responses included two complete remissions (malignant melanoma, TNF dose level I; breast cancer, TNF dose level II), and two disease stabilizations (both malignant melanoma, TNF dose level I). Conclusion: We conclude that the combination of TNF, L-PAM, and WBH is well tolerated at the dose levels studied. The clinical results justify further clinical investigation for this trimodality treatment approach.

Original languageEnglish (US)
Pages (from-to)409-414
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume43
Issue number5
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Lymphotoxin-beta
Melphalan
Fever
Tumor Necrosis Factor-alpha
Toxicity
Therapeutics
Nausea
Vomiting
Melanoma
Herpes Simplex
Leukocyte Count
Intravenous Infusions
Refractory materials
Hypotension
Headache

Keywords

  • Melanoma
  • Melphalan
  • Tumor necrosis factor
  • Whole body hyperthermia

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Robins, H. I., Katschinski, D. M., Longo, W., Grosen, E., Wilding, G., Gillis, W., ... D'Oleire, F. (1999). A pilot study of melphalan, tumor necrosis factor-α and 41.8 °C whole- body hyperthermia. Cancer Chemotherapy and Pharmacology, 43(5), 409-414. https://doi.org/10.1007/s002800050915

A pilot study of melphalan, tumor necrosis factor-α and 41.8 °C whole- body hyperthermia. / Robins, H. I.; Katschinski, D. M.; Longo, W.; Grosen, E.; Wilding, G.; Gillis, W.; Kraemer, C.; Tiggelaar, C. L.; Rushing, D.; Stewart, J. A.; Spriggs, D.; Love, R.; Arzoomanian, R. Z.; Feierabend, C.; Alberti, D.; Morgan, K.; Simon, K.; D'Oleire, F.

In: Cancer Chemotherapy and Pharmacology, Vol. 43, No. 5, 1999, p. 409-414.

Research output: Contribution to journalArticle

Robins, HI, Katschinski, DM, Longo, W, Grosen, E, Wilding, G, Gillis, W, Kraemer, C, Tiggelaar, CL, Rushing, D, Stewart, JA, Spriggs, D, Love, R, Arzoomanian, RZ, Feierabend, C, Alberti, D, Morgan, K, Simon, K & D'Oleire, F 1999, 'A pilot study of melphalan, tumor necrosis factor-α and 41.8 °C whole- body hyperthermia', Cancer Chemotherapy and Pharmacology, vol. 43, no. 5, pp. 409-414. https://doi.org/10.1007/s002800050915
Robins, H. I. ; Katschinski, D. M. ; Longo, W. ; Grosen, E. ; Wilding, G. ; Gillis, W. ; Kraemer, C. ; Tiggelaar, C. L. ; Rushing, D. ; Stewart, J. A. ; Spriggs, D. ; Love, R. ; Arzoomanian, R. Z. ; Feierabend, C. ; Alberti, D. ; Morgan, K. ; Simon, K. ; D'Oleire, F. / A pilot study of melphalan, tumor necrosis factor-α and 41.8 °C whole- body hyperthermia. In: Cancer Chemotherapy and Pharmacology. 1999 ; Vol. 43, No. 5. pp. 409-414.
@article{f202644e19f141c6a26224b8d106bf01,
title = "A pilot study of melphalan, tumor necrosis factor-α and 41.8 °C whole- body hyperthermia",
abstract = "Purpose: To evaluate the feasibility of sequencing (based on preclinical modeling) tumor necrosis factor-α (TNF) at two dose levels with melphalan (L-PAM) and 41.8 °C whole-body hyperthermia (WBH) for 60 min. Patients and methods: Nine patients with refractory cancer were treated from October 1995 to June 1997. The study encompassed a total of 20 trimodality treatment courses. Three patients were treated at TNF dose level I (50 μg/m2) and six patients were treated at TNF dose level II (100 μg/m2). TNF was delivered as a 24-h intravenous infusion, 48 h prior to the combination of L-PAM and WBH; L-PAM was given over 10 min at target temperature at a dose of 17.5 mg/m2 based on a previous phase I WBH/L-PAM trial. WBH was administered with an Aquatherm radiant heat device. Results: Myelosuppression was the major toxicity associated with therapy, but there were no instances of bleeding or neutropenic fevers. Grade 3 thrombocytopenia was seen with 15{\%} of treatments. Regarding absolute neutrophil count, 15{\%} of treatments were associated with grade 3 toxicity, and 45{\%} with grade 4 toxicity, and regarding white blood cell count, 50{\%} of treatments were associated with grade 3 toxicity and 10{\%} with grade 4 toxicity. The myelosuppression observed was equivalent to that seen in our earlier phase I study of WBH and L-PAM (without TNF). Only mild toxicities (grade 1 or 2) were associated with TNF; these were seen with ≤25{\%} of treatments and included nausea, vomiting, diarrhea, fevers, and headache. There were no instances of hypotension. There was no relationship between toxicities observed and the two TNF dose levels. Mild WBH toxicities were seen with less than 15{\%} of treatments; these included nausea, vomiting, and herpes simplex I. Responses included two complete remissions (malignant melanoma, TNF dose level I; breast cancer, TNF dose level II), and two disease stabilizations (both malignant melanoma, TNF dose level I). Conclusion: We conclude that the combination of TNF, L-PAM, and WBH is well tolerated at the dose levels studied. The clinical results justify further clinical investigation for this trimodality treatment approach.",
keywords = "Melanoma, Melphalan, Tumor necrosis factor, Whole body hyperthermia",
author = "Robins, {H. I.} and Katschinski, {D. M.} and W. Longo and E. Grosen and G. Wilding and W. Gillis and C. Kraemer and Tiggelaar, {C. L.} and D. Rushing and Stewart, {J. A.} and D. Spriggs and R. Love and Arzoomanian, {R. Z.} and C. Feierabend and D. Alberti and K. Morgan and K. Simon and F. D'Oleire",
year = "1999",
doi = "10.1007/s002800050915",
language = "English (US)",
volume = "43",
pages = "409--414",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "5",

}

TY - JOUR

T1 - A pilot study of melphalan, tumor necrosis factor-α and 41.8 °C whole- body hyperthermia

AU - Robins, H. I.

AU - Katschinski, D. M.

AU - Longo, W.

AU - Grosen, E.

AU - Wilding, G.

AU - Gillis, W.

AU - Kraemer, C.

AU - Tiggelaar, C. L.

AU - Rushing, D.

AU - Stewart, J. A.

AU - Spriggs, D.

AU - Love, R.

AU - Arzoomanian, R. Z.

AU - Feierabend, C.

AU - Alberti, D.

AU - Morgan, K.

AU - Simon, K.

AU - D'Oleire, F.

PY - 1999

Y1 - 1999

N2 - Purpose: To evaluate the feasibility of sequencing (based on preclinical modeling) tumor necrosis factor-α (TNF) at two dose levels with melphalan (L-PAM) and 41.8 °C whole-body hyperthermia (WBH) for 60 min. Patients and methods: Nine patients with refractory cancer were treated from October 1995 to June 1997. The study encompassed a total of 20 trimodality treatment courses. Three patients were treated at TNF dose level I (50 μg/m2) and six patients were treated at TNF dose level II (100 μg/m2). TNF was delivered as a 24-h intravenous infusion, 48 h prior to the combination of L-PAM and WBH; L-PAM was given over 10 min at target temperature at a dose of 17.5 mg/m2 based on a previous phase I WBH/L-PAM trial. WBH was administered with an Aquatherm radiant heat device. Results: Myelosuppression was the major toxicity associated with therapy, but there were no instances of bleeding or neutropenic fevers. Grade 3 thrombocytopenia was seen with 15% of treatments. Regarding absolute neutrophil count, 15% of treatments were associated with grade 3 toxicity, and 45% with grade 4 toxicity, and regarding white blood cell count, 50% of treatments were associated with grade 3 toxicity and 10% with grade 4 toxicity. The myelosuppression observed was equivalent to that seen in our earlier phase I study of WBH and L-PAM (without TNF). Only mild toxicities (grade 1 or 2) were associated with TNF; these were seen with ≤25% of treatments and included nausea, vomiting, diarrhea, fevers, and headache. There were no instances of hypotension. There was no relationship between toxicities observed and the two TNF dose levels. Mild WBH toxicities were seen with less than 15% of treatments; these included nausea, vomiting, and herpes simplex I. Responses included two complete remissions (malignant melanoma, TNF dose level I; breast cancer, TNF dose level II), and two disease stabilizations (both malignant melanoma, TNF dose level I). Conclusion: We conclude that the combination of TNF, L-PAM, and WBH is well tolerated at the dose levels studied. The clinical results justify further clinical investigation for this trimodality treatment approach.

AB - Purpose: To evaluate the feasibility of sequencing (based on preclinical modeling) tumor necrosis factor-α (TNF) at two dose levels with melphalan (L-PAM) and 41.8 °C whole-body hyperthermia (WBH) for 60 min. Patients and methods: Nine patients with refractory cancer were treated from October 1995 to June 1997. The study encompassed a total of 20 trimodality treatment courses. Three patients were treated at TNF dose level I (50 μg/m2) and six patients were treated at TNF dose level II (100 μg/m2). TNF was delivered as a 24-h intravenous infusion, 48 h prior to the combination of L-PAM and WBH; L-PAM was given over 10 min at target temperature at a dose of 17.5 mg/m2 based on a previous phase I WBH/L-PAM trial. WBH was administered with an Aquatherm radiant heat device. Results: Myelosuppression was the major toxicity associated with therapy, but there were no instances of bleeding or neutropenic fevers. Grade 3 thrombocytopenia was seen with 15% of treatments. Regarding absolute neutrophil count, 15% of treatments were associated with grade 3 toxicity, and 45% with grade 4 toxicity, and regarding white blood cell count, 50% of treatments were associated with grade 3 toxicity and 10% with grade 4 toxicity. The myelosuppression observed was equivalent to that seen in our earlier phase I study of WBH and L-PAM (without TNF). Only mild toxicities (grade 1 or 2) were associated with TNF; these were seen with ≤25% of treatments and included nausea, vomiting, diarrhea, fevers, and headache. There were no instances of hypotension. There was no relationship between toxicities observed and the two TNF dose levels. Mild WBH toxicities were seen with less than 15% of treatments; these included nausea, vomiting, and herpes simplex I. Responses included two complete remissions (malignant melanoma, TNF dose level I; breast cancer, TNF dose level II), and two disease stabilizations (both malignant melanoma, TNF dose level I). Conclusion: We conclude that the combination of TNF, L-PAM, and WBH is well tolerated at the dose levels studied. The clinical results justify further clinical investigation for this trimodality treatment approach.

KW - Melanoma

KW - Melphalan

KW - Tumor necrosis factor

KW - Whole body hyperthermia

UR - http://www.scopus.com/inward/record.url?scp=0033029947&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033029947&partnerID=8YFLogxK

U2 - 10.1007/s002800050915

DO - 10.1007/s002800050915

M3 - Article

VL - 43

SP - 409

EP - 414

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 5

ER -