A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-γ and recombinant interleukin-2 in patients with cancer

C. W. Taylor, E. M. Chase, R. P. Whitehead, J. J. Rinehart, J. A. Neidhart, R. Gonzalez, P. A. Bunn, Evan M Hersh

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Abstract

Thirty-seven patients with advanced malignancies were treated sequentially with recombinant interferon-γ (rIFN-γ) and recombinant interleukin-2 (rIL- 2) in an outpatient dose escalation clinical trial. rIFN-γ (0.1 or 0.25 mg/m2/day) was administered by intramuscular injection, days 1-7 and rIL-2 (12, 18, or 24 x 106IU/m2/day) was administered by a 15-min intravenous bolus, days 8-12. Common toxicities encountered included fever, chills, fatigue, neutropenia, and elevations of SGOT, bilirubin, or creatinine. Hypotension and cardiac and pulmonary toxicities were rare. With repeated cycles of therapy, nausea/vomiting and diarrhea associated with the administration of rIL-2 were seen in greater frequency. There were no treatment-related deaths, and no patient required intensive care unit admission for toxicity management. A complete response was observed in one of 11 patients with renal cancer and a partial response was observed in one of seven patients with malignant melanoma. Due to problems with drug supply, further dose escalation could not be continued, and maximum tolerated doses (MTD) were not determined by strict criteria. However, the combination of rIFN-γ, 0.25 mg/m2/day, and rIL-2, 24 x 106 IU/m2/day, appeared to be beyond the MTD, as three of six patients at this dose level could not complete one cycle of therapy due to toxicity. It is unlikely that higher doses of either agent would be tolerated, and for further study using this schedule, we recommend the doses: rIFN-γ, 0.1 mg/m2/day, and rIL-2, 24 x 106 IU/m2/day.

Original languageEnglish (US)
Pages (from-to)176-183
Number of pages8
JournalJournal of Immunotherapy
Volume11
Issue number3
StatePublished - 1992

Fingerprint

Interferons
Interleukin-2
Maximum Tolerated Dose
Neoplasms
Chills
Kidney Neoplasms
Intramuscular Injections
Aspartate Aminotransferases
Neutropenia
Bilirubin
Hypotension
Nausea
Vomiting
Fatigue
Intensive Care Units
Diarrhea
Melanoma
Creatinine
Appointments and Schedules
Fever

Keywords

  • Interferon-γ
  • Interleukin-2
  • Malignant melanoma
  • Phase I study
  • Renal cancer

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Pharmacology

Cite this

A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-γ and recombinant interleukin-2 in patients with cancer. / Taylor, C. W.; Chase, E. M.; Whitehead, R. P.; Rinehart, J. J.; Neidhart, J. A.; Gonzalez, R.; Bunn, P. A.; Hersh, Evan M.

In: Journal of Immunotherapy, Vol. 11, No. 3, 1992, p. 176-183.

Research output: Contribution to journalArticle

Taylor, CW, Chase, EM, Whitehead, RP, Rinehart, JJ, Neidhart, JA, Gonzalez, R, Bunn, PA & Hersh, EM 1992, 'A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-γ and recombinant interleukin-2 in patients with cancer', Journal of Immunotherapy, vol. 11, no. 3, pp. 176-183.
Taylor, C. W. ; Chase, E. M. ; Whitehead, R. P. ; Rinehart, J. J. ; Neidhart, J. A. ; Gonzalez, R. ; Bunn, P. A. ; Hersh, Evan M. / A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-γ and recombinant interleukin-2 in patients with cancer. In: Journal of Immunotherapy. 1992 ; Vol. 11, No. 3. pp. 176-183.
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abstract = "Thirty-seven patients with advanced malignancies were treated sequentially with recombinant interferon-γ (rIFN-γ) and recombinant interleukin-2 (rIL- 2) in an outpatient dose escalation clinical trial. rIFN-γ (0.1 or 0.25 mg/m2/day) was administered by intramuscular injection, days 1-7 and rIL-2 (12, 18, or 24 x 106IU/m2/day) was administered by a 15-min intravenous bolus, days 8-12. Common toxicities encountered included fever, chills, fatigue, neutropenia, and elevations of SGOT, bilirubin, or creatinine. Hypotension and cardiac and pulmonary toxicities were rare. With repeated cycles of therapy, nausea/vomiting and diarrhea associated with the administration of rIL-2 were seen in greater frequency. There were no treatment-related deaths, and no patient required intensive care unit admission for toxicity management. A complete response was observed in one of 11 patients with renal cancer and a partial response was observed in one of seven patients with malignant melanoma. Due to problems with drug supply, further dose escalation could not be continued, and maximum tolerated doses (MTD) were not determined by strict criteria. However, the combination of rIFN-γ, 0.25 mg/m2/day, and rIL-2, 24 x 106 IU/m2/day, appeared to be beyond the MTD, as three of six patients at this dose level could not complete one cycle of therapy due to toxicity. It is unlikely that higher doses of either agent would be tolerated, and for further study using this schedule, we recommend the doses: rIFN-γ, 0.1 mg/m2/day, and rIL-2, 24 x 106 IU/m2/day.",
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AB - Thirty-seven patients with advanced malignancies were treated sequentially with recombinant interferon-γ (rIFN-γ) and recombinant interleukin-2 (rIL- 2) in an outpatient dose escalation clinical trial. rIFN-γ (0.1 or 0.25 mg/m2/day) was administered by intramuscular injection, days 1-7 and rIL-2 (12, 18, or 24 x 106IU/m2/day) was administered by a 15-min intravenous bolus, days 8-12. Common toxicities encountered included fever, chills, fatigue, neutropenia, and elevations of SGOT, bilirubin, or creatinine. Hypotension and cardiac and pulmonary toxicities were rare. With repeated cycles of therapy, nausea/vomiting and diarrhea associated with the administration of rIL-2 were seen in greater frequency. There were no treatment-related deaths, and no patient required intensive care unit admission for toxicity management. A complete response was observed in one of 11 patients with renal cancer and a partial response was observed in one of seven patients with malignant melanoma. Due to problems with drug supply, further dose escalation could not be continued, and maximum tolerated doses (MTD) were not determined by strict criteria. However, the combination of rIFN-γ, 0.25 mg/m2/day, and rIL-2, 24 x 106 IU/m2/day, appeared to be beyond the MTD, as three of six patients at this dose level could not complete one cycle of therapy due to toxicity. It is unlikely that higher doses of either agent would be tolerated, and for further study using this schedule, we recommend the doses: rIFN-γ, 0.1 mg/m2/day, and rIL-2, 24 x 106 IU/m2/day.

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