Single and Combined (Radiation–Cyclophosphamide) Modality Therapy in Experimental Solid Tumors

Looney, William B.; Hopkins, Harold A.; Kovacs, C. J.; Moore, James; Trefil, James; Rowley, Roy; Carter, W.H.

doi:10.1016/b978-0-12-035410-8.50013-6

Cited by 10 publications

(2 citation statements)

References 65 publications

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“…The clinical investigations at the lnstitut Gustavc Roussy at Villejuif were developed simultaneously but independently from the experimental studies [1][2][3][4][5][6][7][8][9][10]. Alternating RT and CT was based on two clinical observations.…”

Section: Introductionmentioning

confidence: 99%

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Experimental and clinical studies alternating chemotherapy and radiotherapy

1989

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Clinical and experimental results with radiotherapy and chemotherapy for the treatment of cancer emphasize the necessity of giving treatment with both modalities with the greatest intensity possible in the initial phase of induction therapy. This can best be accomplished by utilizing new approaches, such as alternating the chemotherapy with newer methods of delivery of radiotherapy, which has the potential for greater destruction of tumor within acceptable limits of host toxicity. The clinical data from Institut Gustave Roussy, Villejuif, shows that alternating chemotherapy and radiotherapy produced an excellent complete response rate of 79% and a 4 year relapse-free survival rate of 22% in 109 patients with limited small cell lung cancer. Based on 5 year survival criteria, approximately one-fourth of the patients can be considered cured in 1 more year if no further change occurs. The results of the University of Virginia experimental studies have also demonstrated the superiority of alternating cyclophosphamide and radiotherapy in three courses of induction therapy over conventional methods of delivery of the two modalities. Using the experimental solid tumor 3924A, a cure rate of 50% or greater was obtained with this protocol with acceptable toxicity to the host, as opposed to no cures from three or more courses of either modality alone. One of the major deterrents to tumor cure with concomitant chemotherapy and radiotherapy has been excessive toxicity, which can be avoided by temporal separation (+/- 7 days) of the delivery of the two modalities without a significant loss of therapeutic effectiveness. Well-defined clinical protocols to determine how to more effectively interact chemotherapy with radiotherapy offer some of the greatest potential for a more rapid improvement in treatment.

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Section: Introductionmentioning

confidence: 99%

“…The rationale for MFD radiation is that normal tissue recovers more rapidly than tumor tissue [6][7][8][9]. A 50% cure rate could be achieved with 6000 rad given as MFD and alternated with CP, whereas it was necessary to give 11,250 rad as single daily fractions and alternated with CP to achieve a 50% cure rate.…”

Section: Introductionmentioning

confidence: 99%

Experimental and clinical studies alternating chemotherapy and radiotherapy

1989

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Sequencing of drugs and radiation. The integrated alternating regimen

Tubiana

Arriagada

Cosset

1985

Cancer

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The association of radiotherapy (RT) and chemotherapy (CT) constitutes one of the main avenues for research in therapeutic oncology. This association has two aims: (1) increase in control rate of primary tumor (this requires either the potentiation of one of the two modalities by the other or the additivity of their effect on tumor cells without a parallel increase in the toxic effects on critical normal tissues); (2) spatial cooperation (RT being used for the control of the primary tumor or of the sanctuaries, and CT for the control of the disseminated disease). In these two strategies, RT and CT should be given up to full doses in order to be effective. The main risk is an increase in the number and severity of the early and late side effects. To circumvent this problem, two possibilities are being explored: (1) use of drugs without serious toxic effects on those critical tissues which are included in the irradiated volume; and (2) avoidance of concomitant administration and introduction of a sufficiently long‐time gap between the completion of one modality and initiation of the other. However, in such sequential treatment, a delay of CT until after the completion of RT, or an interruption of CT cycle during the course of RT, allows the occult metastases to increase in size; a similar delay in initiation of RT is also detrimental, as drugs are often not effective on bulky tumors. Moreover, under CT, the cells which are resistant to the cytotoxic drugs may disseminate and initiate chemoresistant metastases. Taking these disadvantages into account, a treatment protocol was proposed in 1980 in which CT and RT are given alternately, without undue delay. Chemotherapy is started with the usual scheduling of one cycle every month. Radiotherapy courses are interdigitated between CT cycles. Each course is initiated 1 week after interrupting CT and continued until 1 week before beginning the subsequent cycle of chemotherapy, and so on until completion of RT. Such split‐course RT should have an effect on a tumor comparable to that of a conventional fractionation. This protocol has been used on 24 patients with non‐Hodgkin's lymphoma (NHL) of diffuse histology, and 63 patients with small cell carcinoma of the lung. The 2‐year relapse‐free survivals are promising (in clinical stage II NHL of diffuse histology, 75%; and in small cell lung carcinomas, 33%). The early and late tolerances are satisfactory and no untoward complications have been observed.

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Advances in pediatric radiotherapy in the last ten years and future proposals

Fryer

1986

Cancer

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Advances made can be divided into five main categories. Firstly, the problem of geographic miss which has been reduced by delivering effective radiation doses with greater precision. This has been accomplished with more sophisticated diagnostic and therapeutic equipment, immobilization techniques and computerized treatment planning. Second is the recognition of the interplay of radiation and chemotherapy on normal tissue tolerance and local tumor control. This interaction has necessitated reduction in both dose and volume of irradiation. Third is the use of wide field irradiation as a systemic treatment. Fourthly, the utilization of cooperative group trials to define the role of irradiation. Finally, with the improvement in survival has come the recognition of late effects of irradiation in the growing child and the means of reducing such effects. The current role of radiation therapy in childhood malignancies is summarized, controversies are identified, and future prospects explored.

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Single and Combined (Radiation–Cyclophosphamide) Modality Therapy in Experimental Solid Tumors

Cited by 10 publications

References 65 publications

Experimental and clinical studies alternating chemotherapy and radiotherapy

Experimental and clinical studies alternating chemotherapy and radiotherapy

Sequencing of drugs and radiation. The integrated alternating regimen

Advances in pediatric radiotherapy in the last ten years and future proposals

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