Efficacy of continuous treatment with radiation in a rat brain-tumor model

Restricted access

✓ Rats bearing intracerebral 9L/Ro tumors were treated with 10 daily fractions of cesium-137 γ-rays, BCNU, or combinations of these two agents beginning on either Day 10 or Day 12 after implantation. The treatments were administered either 5 days/week for 2 weeks, with the weekend off, or 10 consecutive days. The median day of death for untreated tumor-bearing rats was Day 15, so Day 12 tumors can be considered late tumors and Day 10 tumors can be considered moderately early. Although all single- and multiple-agent treatments significantly (p < 0.05) increased the lifespan of tumor-bearing rats over that of the untreated controls, and all multiple-agent schedules significantly (p < 0.05) increased the lifespan over that of the single-agent therapies, none of the 10 consecutive day schedules increased the lifespan of tumorbearing rats significantly (p > 0.2) over that obtained with the 5-day/week schedules. Thus, the evidence from this tumor model suggests that no significant improvement in lifespan would be expected if malignant brain tumors were treated with radiation 7 days a week, either alone or in combination with chemotherapeutic agents such as BCNU.

Article Information

Address reprint requests to: Kenneth T. Wheeler, Ph.D., Box 704, Cancer Center, University of Rochester, 601 Elmwood Avenue, Rochester, New York 14642.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Kaplan-Meier plots of intracerebral 9L/Ro tumor-bearing rats treated on either 10 consecutive days or 5 days per week for 2 weeks with 260 rads of γ-rays or combinations of 2 mg/kg/day of BCNU 16 hours before each 260-rad treatment of γ-rays. Each group contained 10 rats, and treatments were begun either 10 or 12 days after implantation. Top Panel: Day 10 tumors. Continuous line: untreated controls; dashed line: 260 rads/day of γ-rays given 5 days per week for 2 weeks; dotted line: 260 rads/day of γ-rays given 10 consecutive days. Middle Panel: Day 10 tumors. Dotted line: 2 mg/kg/day of BCNU 16 hours before 260 rads/day of γ-rays given 5 days per week for 2 weeks. Continuous line: 2 mg/kg/day of BCNU 16 hours before 260 rads/day of γ-days given 10 consecutive days. Lower Panel: Same as middle panel except that Day 12 tumors were treated. Note the x-axis of the upper panel is different from that of the lower two panels.

References

  • 1.

    Barker MHoshino TGurcay Oet al: Development of an animal brain tumor model and its response to therapy with 1,3-bis(2-chloroethyl)-l-nitrosourea. Cancer Res 33:9769891973Barker M Hoshino T Gurcay O et al: Development of an animal brain tumor model and its response to therapy with 13-bis(2-chloroethyl)-l-nitrosourea. Cancer Res 33:976–989 1973

    • Search Google Scholar
    • Export Citation
  • 2.

    Barker MHoshino TWheeler KTet al: Chemotherapeutic implications of early tumor cell growth in an animal brain-tumor model. JNCI 54:8518531975Barker M Hoshino T Wheeler KT et al: Chemotherapeutic implications of early tumor cell growth in an animal brain-tumor model. JNCI 54:851–853 1975

    • Search Google Scholar
    • Export Citation
  • 3.

    Cox DR: Regression models and life tables. J R Stat Soc B 26:1031101972Cox DR: Regression models and life tables. J R Stat Soc B 26:103–110 1972

    • Search Google Scholar
    • Export Citation
  • 4.

    Leith JTSchilling WAWheeler KT: Cellular radiosensitivity of a rat brain tumor. Cancer 35:154515501975Leith JT Schilling WA Wheeler KT: Cellular radiosensitivity of a rat brain tumor. Cancer 35:1545–1550 1975

    • Search Google Scholar
    • Export Citation
  • 5.

    Levin VAStearns JByrd Aet al: The effect of phenobarbital pretreatment on the antitumor activity of 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU), 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) and 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea (PCNU), and on the plasma pharmacokinetics and biotransformation of BCNU. J Pharmacol Exp Ther 208:161979Levin VA Stearns J Byrd A et al: The effect of phenobarbital pretreatment on the antitumor activity of 13-bis(2-chloroethyl)-l-nitrosourea (BCNU) 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) and 1-(2-chloroethyl)-3-(26-dioxo-3-piperidyl)-1-nitrosourea (PCNU) and on the plasma pharmacokinetics and biotransformation of BCNU. J Pharmacol Exp Ther 208:1–6 1979

    • Search Google Scholar
    • Export Citation
  • 6.

    Mantel N: Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:1631701966Mantel N: Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:163–170 1966

    • Search Google Scholar
    • Export Citation
  • 7.

    Walker MDAlexander E JrHunt WEet al: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 49:3333431978Walker MD Alexander E Jr Hunt WE et al: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 49:333–343 1978

    • Search Google Scholar
    • Export Citation
  • 8.

    Walker MDGehan EA: Clinical studies in malignant gliomas and their treatment with nitrosoureas. Cancer Treat Rep 60:7137161976Walker MD Gehan EA: Clinical studies in malignant gliomas and their treatment with nitrosoureas. Cancer Treat Rep 60:713–716 1976

    • Search Google Scholar
    • Export Citation
  • 9.

    Walker MDStrike TASheline GE: An analysis of dose-effect relationships in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys 5:172517311979Walker MD Strike TA Sheline GE: An analysis of dose-effect relationships in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys 5:1725–1731 1979

    • Search Google Scholar
    • Export Citation
  • 10.

    Wheeler KTKaufman K: Brain tumor therapy: prospects for combining BCNU with conventional radiotherapy schedules. Int J Radiat Oncol Biol Phys (In press)Wheeler KT Kaufman K: Brain tumor therapy: prospects for combining BCNU with conventional radiotherapy schedules. Int J Radiat Oncol Biol Phys (In press)

    • Search Google Scholar
    • Export Citation
  • 11.

    Wheeler KTKaufman K: Influence of fractionation schedules on the response of a rat brain tumor to therapy with BCNU and radiation. Int J Radiat Oncol Biol Phys 6:8458491980Wheeler KT Kaufman K: Influence of fractionation schedules on the response of a rat brain tumor to therapy with BCNU and radiation. Int J Radiat Oncol Biol Phys 6:845–849 1980

    • Search Google Scholar
    • Export Citation
  • 12.

    Wheeler KTKaufman KFeldstein M: Response of a rat brain tumor to fractionated therapy with low doses of BCNU and irradiation. Int J Radiat Oncol Biol Phys 5:155315571979Wheeler KT Kaufman K Feldstein M: Response of a rat brain tumor to fractionated therapy with low doses of BCNU and irradiation. Int J Radiat Oncol Biol Phys 5:1553–1557 1979

    • Search Google Scholar
    • Export Citation
  • 13.

    Wheeler KTWallen CA: Is cell survival a determinant of the in situ response of 9L tumors? Br J Cancer 41( Suppl IV): 2993031980Wheeler KT Wallen CA: Is cell survival a determinant of the in situ response of 9L tumors? Br J Cancer 41(Suppl IV):299–303 1980

    • Search Google Scholar
    • Export Citation

TrendMD

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 67 67 3
Full Text Views 78 71 0
PDF Downloads 49 38 0
EPUB Downloads 0 0 0

PubMed

Google Scholar