The effect of varying the time between irradiation and cyclophosphamide on growth response of hepatoma 3924A

Hopkins, Harold A.; Ritenour, E. Russell; MacLeod, M. S.; Looney, William B.

doi:10.1016/0360-3016(79)90748-x

Cited by 13 publications

(3 citation statements)

References 4 publications

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“…7), with three intermittent MFD courses giv- en on days 0--1, 11 and 12, and 22 and 23 ( Fig. 8) [23]. Neither radiation given alone as daily fractions nor intermittent MFD was effective in controlling tumor growth.…”

Section: Three Courses Of' Daily Radiation Fractions Alone Versus Thrmentioning

confidence: 99%

“…One of the most significant clinical ramifications of these findings is that relatively long periods of time (7 days) can elapse between modalities without loss of therapeutic effectiveness. Earlier data [10,23] showed no consistent differences in effectiveness when the two modalities were given together or separated by 1, 2, 3, 4 or 7 days. Intervals of 11 and 15 days between modalities were less effective in controlling growth of tumor.…”

Section: Three Courses Of Daily or Mfd Radiationmentioning

confidence: 99%

“…Cyclophosphamide (150 mg/kg) was given on days 10, 21, and 32 for only the combined group. (From Looney and Hopkins[23]. )…”

mentioning

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: Three Courses Of' Daily Radiation Fractions Alone Versus Thrmentioning

confidence: 99%

Section: Three Courses Of Daily or Mfd Radiationmentioning

confidence: 99%

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Experimental and clinical studies alternating chemotherapy and radiotherapy

1989

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Effect of timing and sequence of hyperthermia and cyclophosphamide on a neurogenic rat tumor (BT4A) in vivo

Dahl¹,

Mella²

1983

Cancer

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The interaction of hyperthermia (HT) 1 hour at 44.0°C and cyclophosphamide (CP) 200 mg/kg was studied in vivo in a solid transplantable neurogenic rat tumor (BT4A) in the foot of BD IX rats. HT was given by water bath heating. When both modalities were close in time (CP immediately before HT or 1 hour before HT), an enhanced effect with complete regression and cure of tumors was seen. This could not be obtained with either modality alone. Extending the interval between treatments within 24 hours, an effect equal to the sum of each modality was obtained when HT was given before CP, while HT after CP was less effective. Timing and sequence may be critical factors for the optimal combination of HT and cytotoxic drugs.

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Rationale for different chemotherapeutic and radiation therapy strategies in cancer management

Looney

Hopkins

1991

Cancer

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The two primary therapeutic strategies in cancer have been to give either chemotherapy and radiation therapy together or give a complete course of one treatment modality before starting the second. Clinical studies show that toxicity has been one of the major deterrents to substantial improvements in cancer management when the two modalities are administered together. On the other hand, the prolonged time necessary to administer all of one modality followed by the other makes it likely that repopulation of the tumor during sequential treatment will diminish therapeutic effectiveness. A third strategy of giving chemotherapy and radiation therapy has been developed. This new regimen was designed to give chemotherapy initially, maintain the chemotherapy schedule to avoid any reduction in its effectiveness, and add radiation therapy as early as possible in between courses of chemotherapy to minimize the development of cross resistance. One of the primary objectives of alternating chemotherapy and radiation therapy is to increase the therapeutic index by reducing toxicity without a significant reduction in therapeutic effectiveness. Recent clinical, experimental, and theoretic results with radiation therapy and chemotherapy for cancer management emphasize the necessity of giving both modalities with the greatest intensity possible in the initial phase of induction therapy. Cancer treatment scheduling determines the toxicity and thereby limits the dose intensity that can be tolerated. Scheduling may also govern the antitumor effect directly; however, normal host tissue makes the determination of the direct effects on the tumor difficult, if not impossible, in clinical studies. Well-defined experimental solid-tumor systems provide the means for determining directly the relationship between toxicity and antitumor effects in relation to tumor burden and total therapeutic dose. In addition, its relationship to dose intensity and scheduling can be determined by the using more sophisticated research techniques, such as response surface methods. Well-defined clinical protocols to determine how to interact chemotherapy with radiation therapy more effectively hold considerable potential for rapid improvement in treatment of radiosensitive and chemosensitive cancers.

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The effect of varying the time between irradiation and cyclophosphamide on growth response of hepatoma 3924A

Cited by 13 publications

References 4 publications

Experimental and clinical studies alternating chemotherapy and radiotherapy

Experimental and clinical studies alternating chemotherapy and radiotherapy

Effect of timing and sequence of hyperthermia and cyclophosphamide on a neurogenic rat tumor (BT4A) in vivo

Rationale for different chemotherapeutic and radiation therapy strategies in cancer management

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