Pilot study of local hyperthermia, radiation therapy, etanidazole, and cisplatin for advanced superficial tumours

B. A. Bornstein, T. S. Herman, J. L. Hansen, L. Buswell, P. S. Zouranjian, S. M. Fraser, B. A. Teicher, G. K. Svensson, C. N. Coleman

Research output: Contribution to journalArticle

Abstract

Five patients (six hyperthermia sites) with advanced superficial tumours were treated with combined etanidazole, cisplatin, local hyperthermia, and radiation therapy as part of a Phase I pilot study. Treatment was given once weekly and consisted of etanidazole 3 gm/m2 IV bolus, cisplatin 50 mg/m2 IV bolus, hyperthermia for 60 min with a target temperature of 43°C, and radiation therapy 500 cGy/fraction (median total dose 3000 cGy) for a total of six weeks. Blood levels of etanidazole were taken during treatment at week 1 and week 4. Etanidazole drug exposure was calculated using the trapezoidal rule and expressed as the area under the curve (AUC) of plasma concentration X time. Five of six treatment sites had received prior irradiation. Prior chemotherapy had been given in three patients and tamoxifen therapy given in the other two patients. The median follow-up time is 34 months; 3/5 patients have died of disease. The most significant toxicity was grade I or II nausea and vomiting associated with 19/32 treatments (59% and a second degree burn in 2/6 fields. None of the five patients experienced peripheral neuropathy, skin ulceration, or needed surgical repair. In addition, there was mild renal toxicity; pharmacokinetic analysis showed a 28-75% increase in the week 1 to week 4 AUC in three patients, all of whom had a decrease in creatinine clearance over the same time of 15-47% This pilot study suggests this combined modality therapy can be delivered without major complications and that renal function, determined by creatinine clearance, affects clearance of etanidazole and alters the AUC. Therefore, monitoring renal function is important in patients receiving etanidazole in addition to other nephrotoxic agents such as cisplatin. The impact of etanidazole on the therapeutic index of hyperthermia, radiation therapy and cisplatin may be worthy of study, especially since a positive interaction between these modalities is found in laboratory models.

Original languageEnglish (US)
Pages (from-to)489-499
Number of pages11
JournalInternational Journal of Hyperthermia
Volume11
Issue number4
DOIs
StatePublished - 1995
Externally publishedYes

Fingerprint

Etanidazole
Induced Hyperthermia
Cisplatin
Radiotherapy
Neoplasms
Area Under Curve
Kidney
Creatinine
Fever
Therapeutics
Combined Modality Therapy
Peripheral Nervous System Diseases
Tamoxifen
Nausea
Vomiting
Pharmacokinetics
Drug Therapy
Skin
Temperature

Keywords

  • Chemotherapy
  • Combined modality
  • Etanidazole
  • Hyperthermia
  • Radiation therapy

ASJC Scopus subject areas

  • Cancer Research
  • Physiology
  • Radiological and Ultrasound Technology
  • Physiology (medical)

Cite this

Bornstein, B. A., Herman, T. S., Hansen, J. L., Buswell, L., Zouranjian, P. S., Fraser, S. M., ... Coleman, C. N. (1995). Pilot study of local hyperthermia, radiation therapy, etanidazole, and cisplatin for advanced superficial tumours. International Journal of Hyperthermia, 11(4), 489-499. https://doi.org/10.3109/02656739509022484

Pilot study of local hyperthermia, radiation therapy, etanidazole, and cisplatin for advanced superficial tumours. / Bornstein, B. A.; Herman, T. S.; Hansen, J. L.; Buswell, L.; Zouranjian, P. S.; Fraser, S. M.; Teicher, B. A.; Svensson, G. K.; Coleman, C. N.

In: International Journal of Hyperthermia, Vol. 11, No. 4, 1995, p. 489-499.

Research output: Contribution to journalArticle

Bornstein, BA, Herman, TS, Hansen, JL, Buswell, L, Zouranjian, PS, Fraser, SM, Teicher, BA, Svensson, GK & Coleman, CN 1995, 'Pilot study of local hyperthermia, radiation therapy, etanidazole, and cisplatin for advanced superficial tumours', International Journal of Hyperthermia, vol. 11, no. 4, pp. 489-499. https://doi.org/10.3109/02656739509022484
Bornstein, B. A. ; Herman, T. S. ; Hansen, J. L. ; Buswell, L. ; Zouranjian, P. S. ; Fraser, S. M. ; Teicher, B. A. ; Svensson, G. K. ; Coleman, C. N. / Pilot study of local hyperthermia, radiation therapy, etanidazole, and cisplatin for advanced superficial tumours. In: International Journal of Hyperthermia. 1995 ; Vol. 11, No. 4. pp. 489-499.
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abstract = "Five patients (six hyperthermia sites) with advanced superficial tumours were treated with combined etanidazole, cisplatin, local hyperthermia, and radiation therapy as part of a Phase I pilot study. Treatment was given once weekly and consisted of etanidazole 3 gm/m2 IV bolus, cisplatin 50 mg/m2 IV bolus, hyperthermia for 60 min with a target temperature of 43°C, and radiation therapy 500 cGy/fraction (median total dose 3000 cGy) for a total of six weeks. Blood levels of etanidazole were taken during treatment at week 1 and week 4. Etanidazole drug exposure was calculated using the trapezoidal rule and expressed as the area under the curve (AUC) of plasma concentration X time. Five of six treatment sites had received prior irradiation. Prior chemotherapy had been given in three patients and tamoxifen therapy given in the other two patients. The median follow-up time is 34 months; 3/5 patients have died of disease. The most significant toxicity was grade I or II nausea and vomiting associated with 19/32 treatments (59{\%} and a second degree burn in 2/6 fields. None of the five patients experienced peripheral neuropathy, skin ulceration, or needed surgical repair. In addition, there was mild renal toxicity; pharmacokinetic analysis showed a 28-75{\%} increase in the week 1 to week 4 AUC in three patients, all of whom had a decrease in creatinine clearance over the same time of 15-47{\%} This pilot study suggests this combined modality therapy can be delivered without major complications and that renal function, determined by creatinine clearance, affects clearance of etanidazole and alters the AUC. Therefore, monitoring renal function is important in patients receiving etanidazole in addition to other nephrotoxic agents such as cisplatin. The impact of etanidazole on the therapeutic index of hyperthermia, radiation therapy and cisplatin may be worthy of study, especially since a positive interaction between these modalities is found in laboratory models.",
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AU - Herman, T. S.

AU - Hansen, J. L.

AU - Buswell, L.

AU - Zouranjian, P. S.

AU - Fraser, S. M.

AU - Teicher, B. A.

AU - Svensson, G. K.

AU - Coleman, C. N.

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AB - Five patients (six hyperthermia sites) with advanced superficial tumours were treated with combined etanidazole, cisplatin, local hyperthermia, and radiation therapy as part of a Phase I pilot study. Treatment was given once weekly and consisted of etanidazole 3 gm/m2 IV bolus, cisplatin 50 mg/m2 IV bolus, hyperthermia for 60 min with a target temperature of 43°C, and radiation therapy 500 cGy/fraction (median total dose 3000 cGy) for a total of six weeks. Blood levels of etanidazole were taken during treatment at week 1 and week 4. Etanidazole drug exposure was calculated using the trapezoidal rule and expressed as the area under the curve (AUC) of plasma concentration X time. Five of six treatment sites had received prior irradiation. Prior chemotherapy had been given in three patients and tamoxifen therapy given in the other two patients. The median follow-up time is 34 months; 3/5 patients have died of disease. The most significant toxicity was grade I or II nausea and vomiting associated with 19/32 treatments (59% and a second degree burn in 2/6 fields. None of the five patients experienced peripheral neuropathy, skin ulceration, or needed surgical repair. In addition, there was mild renal toxicity; pharmacokinetic analysis showed a 28-75% increase in the week 1 to week 4 AUC in three patients, all of whom had a decrease in creatinine clearance over the same time of 15-47% This pilot study suggests this combined modality therapy can be delivered without major complications and that renal function, determined by creatinine clearance, affects clearance of etanidazole and alters the AUC. Therefore, monitoring renal function is important in patients receiving etanidazole in addition to other nephrotoxic agents such as cisplatin. The impact of etanidazole on the therapeutic index of hyperthermia, radiation therapy and cisplatin may be worthy of study, especially since a positive interaction between these modalities is found in laboratory models.

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