Solid tumor models for the assessment of different treatment modalities: XXI. Comparison of different radiation dose schedules alone or in combination with cyclophosphamide

Looney, William B.; Longerbeam, Mark B.; Hopkins, Harold A.; Carter, Walter H.

doi:10.1002/1097-0142(19830315)51:6<1012::aid-cncr2820510608>3.0.co;2-#

Cited by 10 publications

(2 citation statements)

References 9 publications

(3 reference statements)

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“…The effect of the combination was not dependent on the dose of cisplatin but did depend on the dose of radiation. A similar dose-dependent enhancement of the antitumour efTect by radiation was reported by Looney et al who used rat hepatoma 3924A and the administration ofcyclophosphamide (4).…”

Section: Discussionsupporting

confidence: 74%

Combined Treatment with Cisplatin and Radiation Therapy for Mouse CI 300 Neuroblastoma

Ishimaru¹,

Nakagawara²,

Zaizen³

et al. 1985

Eur J Pediatr Surg

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The efficacy of the combined treatment of cisplatin and radiation therapy for mouse C1 300 neuroblastoma was studied. Intraperitoneal cisplatin injections and/or radiation were given from 7 to 21 days after inoculation of the tumor cells into the thigh region of A/Jax mice. The combination of 15 Gy radiation and 6 mg/kg cisplatin had an additive effect on both tumour growth delay and survival rate, while that of 30 Gy radiation and 6 mg/kg cisplatin had a synergistic effect. The efficacy of the combined therapy was dependent on the dose of radiation but not on the dose of cisplatin. The normal skin of the mouse was damaged in the similar pattern with both treatments. Thus, cisplatin has a potent radiosensitising effect in the treatment of mouse neuroblastoma.

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Section: Discussionsupporting

confidence: 74%

Combined Treatment with Cisplatin and Radiation Therapy for Mouse CI 300 Neuroblastoma

Ishimaru¹,

Nakagawara²,

Zaizen³

et al. 1985

Eur J Pediatr Surg

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“…'^ Our data and the results of other investigators indicate that radiation combined with CP results in no increase in skin reaction compared with radiation alone. 3 3 2 2 3 2 3 Major increases in the time interval between administration of the two modalities from 1 to 7 days and the overall time of delivery of the 3 courses from 21 to 35 days did not result in major loss of therapeutic effectiveness. Cure rates of 50% or greater could be maintained even though treatment was given over much longer periods of time.…”

Section: Days After Initiation Of Treatmentmentioning

confidence: 97%

Solid tumor models for the assessment of different treatment modalities. XXII. The alternate utilization of radiotherapy and chemotherapy

Looney

Hopkins

Carter

1984

Cancer

Self Cite

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Major increases in the time between administration of two modalities, radiation and cyclophosphamide (CP), from 1 to 7 days and in the overall time of delivery of 3 courses of combined therapy from 24 to 35 days were carried out in rats with hepatoma 3924A without major loss of therapeutic effectiveness. Cure rates of 50% or greater could be maintained even though treatment was given over much longer time periods. The radiation was given as hyperfractionated, split‐course schedules which were devised by increasing the number of 250 rad fractions over a 2‐day period. In one series of experiments these 2‐day schedules were given at 11‐day intervals for 3 courses on days 0 and 1, 11 and 12, 22 and 23; and CP (150 mg/kg) was given 1 day after each of the 3 radiation courses on days 2, 13, and 24. In the second series of experiments radiation was given on days 0 and 1, 14 and 15, 28 and 29; and this was alternated with 3 single doses of CP given 1 week after each of the 3 courses of radiation, on days 7, 21 and 35. Increasing the total radiation dose from 6000 to 7500 rad in the series given CP 1 day after each of three courses of radiation results in an increase in total tumor cure rates from 50% to 60%. The tumor cure rate in the series given CP 7 days after radiation increased from 10% to 70% when the total radiation dose was increased from 6000 to 7500 rad. Increasing the total radiation dose from 6000 to 7500 rad increased the magnitude of the acute skin reaction as well as the duration of recovery. However, the skin reactions for both the 6000 and 7500 rad were acceptable. Host toxicity and normal tissue reaction were within acceptable limits for both modalities. The results of these studies, therefore, indicate that excessive toxicity, one of the major deterrents to the effective combined utilization of these two primary means of cancer management, may be avoided by temporal separation of delivery while maintaining tumor cure rates of 50% or greater.

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Biological basis for the interaction of chemotherapeutic agents and radiation therapy

Fu¹

1985

Cancer

132

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The ultimate goal of combining chemotherapy and radiotherapy is to improve the therapeutic ratio. When chemotherapy is combined with radiotherapy, improved therapeutic effects may occur as a result of the following: (1) spatial cooperation; (2) enhancement of tumor response with less or no enhancement of normal tissue injury, and (3) diminution of normal tissue injury with less or no diminution of tumor response. Possible mechanisms of interaction between chemotherapeutic agents and radiation that result in an enhanced effect include (1) changes in the slope of the dose response curve, (2) decreased accumulation or inhibition of repair of sublethal damage, (3) decreased recovery from potentially lethal damage, (4) perturbation in cell kinetics with an increase of proportion of cells in the sensitive cell cycle phase and proliferative state, (5) decreased tumor bulk and improved blood supply leading to reoxygenation and recruitment and increased radiosensitivity and chemosensitivity, and (6) increased drug delivery and uptake. The combined effects may be influenced by (1) tumor and normal tissue type, (2) drug type, (3) drug dose and schedule, (4) time sequence between drug and radiation administration, (5) radiation dose and fractionation schedule, and (6) radiation dose rate. Most experimental and clinical data suggest that enhanced tumor effects most often result from simple additivity and therefore do not require direct interaction between drug and radiation, whereas enhanced normal tissue effects are observed most often when drugs are administered in close temporal proximity to radiation. Thus, for the optimal therapeutic effect, it would seem more advantageous to administer chemotherapeutic drugs and radiation in a sequential or alternating manner rather than simultaneously.

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Solid tumor models for the assessment of different treatment modalities: XXI. Comparison of different radiation dose schedules alone or in combination with cyclophosphamide

Cited by 10 publications

References 9 publications

Combined Treatment with Cisplatin and Radiation Therapy for Mouse CI 300 Neuroblastoma

Combined Treatment with Cisplatin and Radiation Therapy for Mouse CI 300 Neuroblastoma

Solid tumor models for the assessment of different treatment modalities. XXII. The alternate utilization of radiotherapy and chemotherapy

Biological basis for the interaction of chemotherapeutic agents and radiation therapy

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