Hyperbaric oxygen therapy for carcinoma of the cervix—Stages IIB, IIIA, IIIB and IVA: Results of a randomized study by the radiation therapy oncology group

Brady, Luther W.; Plenk, Henry P.; Hanley, James A.; Glassburn, John R.; Krämer, Simon; Parker, Robert G.

doi:10.1016/0360-3016(81)90149-8

Cited by 46 publications

(13 citation statements)

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“…Factors contributing to tumour hypoxia are increased oxygen consumption as a result of unrestricted cell proliferation (Nordsmark et al, 1996b) and inefficient oxygen delivery as a consequence of widely variable interstitial pressure gradients and irregular microvessel distribution (Jain, 1988). Different attempts to increase oxygen delivery to tumours have included the use of blood flow modifiers (Horsman et al, 1991) and the use of hyperbaric oxygen (Fletcher et al, 1977;Ward and Dixon, 1979;Dische, 1983;Brady et al, 1981). Neither approach has demonstrated consistent success in clinical trials to warrant therapeutic application outside investigative protocols.…”

Section: Discussionmentioning

confidence: 99%

“…A meta-analysis of randomized studies involving hypoxic cell radiosensitization via nitroimidazoles revealed significant, albeit small, improvement in local control and survival in patients with head and neck and bladder carcinomas (Overgaard, 1994). The use of hyperbaric oxygen as an adjuvant to radiotherapy for locally advanced cervical cancer was evaluated in several randomized studies, but a benefit was not consistently observed (Fletcher et al, 1977;Ward and Dixon, 1979;Dische, 1983;Brady et al, 1981). An alternative approach to improved oxygen delivery to tumour tissues is to exploit the enormous reservoir of oxygen that remains bound to Hb even after passage of blood through the capillary bed.…”

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confidence: 99%

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RSR13, an allosteric effector of haemoglobin, and carbogen radiosensitize FSAII and SCCVII tumours in C3H mice

et al. 1999

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Summary Pre-clinical evaluation has demonstrated that 2- [4-(((3,5-dimethylanilino)carbonyl)methyl)phenoxy]-2-methylpropionic acid (RSR13) acts as an allosteric effector of haemoglobin (Hb). RSR13 binding to Hb results in decreased haemoglobin-oxygen (Hb-O 2 ) affinity, improved tumour oxygenation, and enhanced radiation-induced cell killing in several experimental tumour systems. In the present work, ex vivo clonogenic survival analyses are applied in two murine tumour systems to characterize the relationship between the magnitude of decrease in Hb-O 2 affinity and radiosensitization, the influence of inspired pO 2 upon this effect, and the efficacy of combining RSR13 and radiation during a course of repeated radiation exposures. For FSaII tumours in C3H mice breathing air, 100 mg kg -1 RSR13 administered intraperitoneally produced an enhancement ratio (ER) of 1.3, but there was marked desensitization at a RSR13 dose of 300 mg kg -1 (ER 0.6). The most likely reason for the increased radioresistance was insufficient oxygen loading of Hb in the pulmonary circulation due to reduced haemoglobin-oxygen affinity because carbogen breathing combined with 300 mg kg -1 RSR13 reversed the effect and produced an ER of 1.8. In SCCVII tumours in C3H mice irradiated with eight fractions of 2.5 Gy over 4 days, the surviving fraction was reduced to 58-67% of control values when RSR13 was combined with radiation on days 1 and 2, days 3 and 4, or days 1-4. These results confirm that combining RSR13 and irradiation within a fractionated course of clinically relevant low-dose exposures provides significant radiosensitization. Additional preclinical experimentation is needed to define better the optimum dose-scheduling conditions for clinical applications.Keywords: RSR13; haemoglobin-oxygen affinity; allosteric effectors of haemoglobin; tumour hypoxia; radiosensitizer 814British Journal of Cancer (1999) 79(5/6), 814-820 © 1999 Cancer Research Campaign Article no. bjoc.1998 Received 11 To optimize the efficacy of RSR13 combined with radiotherapy, it is important to characterize the quantitative relationship between increases in p50 and radiation-induced cytotoxicity and the effect of inspired pO 2 upon this effect. It is also essential to establish with greater certainty the enhancement of tumour radiosensitivity within dose schedules that combine RSR13 with repeated radiation exposures, as is typical for a course of fractionated radiotherapy. The present work addresses these issues using highly sensitive ex vivo clonogenic survival analyses in two syngeneic murine tumour systems, both established models of tumour hypoxia (Okunieff et al, 1986;Brown and Lemmon, 1990). For the murine FSaII fibrosarcoma, single-exposure radiation dose-response analyses were generated at different doses of RSR13 and air or carbogen breathing. The schedule dependence of RSR13 combined with repeated radiation exposures in the therapeutic dose range was investigated using SCCVII tumours. MATERIALS AND METHODS Preparation, dosage and administration of RS...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

RSR13, an allosteric effector of haemoglobin, and carbogen radiosensitize FSAII and SCCVII tumours in C3H mice

et al. 1999

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“…[12][13][14] To decrease the local recurrence, several strategies were adopted. For example, hypoxic sensitizers, 15,16 hyperbaric oxygen, 17 radioprotector, 18 neutron therapy, 19 hyperthermia, 20 and hyperfractionation 21 were attempted to decrease the local recurrence. In the 1990s, through the development of new chemotherapy drugs, the addition of chemotherapy to radiation was suggested to decrease the rate of local recurrence.…”

Section: Discussionmentioning

confidence: 99%

The efficacy of concurrent cisplatin and 5-flurouracil chemotherapy and radiation therapy for locally advanced cancer of the uterine cervix

et al. 2008

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Objective: To evaluate the efficacy of concurrent chemoradiation (CCRT) using 5-flurouracil (5-FU) and cisplatin for locally advanced cervical cancer. Methods: We reviewed the medical records of 57 patients with locally advanced cervical cancer (stage IIB-IVA and bulky IB2-IIA tumor) who underwent the CCRT at Dong-A University Hospital from January 1997 to June 2007. The CCRT consisted of 5-FU, cisplatin and pelvic radiation. Every three weeks, 75 mg/m 2 cisplatin was administered on the first day of each cycle and 5-FU was infused at the dose of 1,000 mg/m 2 /d from the second day to the fifth day of each cycle. Radiation was administered to the pelvis at a daily dose of 1.8 Gy for five days per week until a medium accumulated dose reached to 50.4 Gy. If necessary, the radiation field was extended to include paraaortic lymph nodes. Consolidation chemotherapy was performed using 5-FU and cisplatin. Results: Fifty-seven patients were enrolled and the median follow-up duration was 53 months (range 7-120 months). The overall response rate was 91.5% (74% complete response and 17.5% partial response). The 5-year overall survival and 3-year progression free survival rates were 69.4% and 74.9%, respectively. During the follow-up period (median 23 months, range 7-60 months), fourteen patients were diagnosed as recurrent disease. Conclusion: CCRT with 5-FU and cisplatin which is the primary treatment for patients with locally advanced cervical cancer was effective and well tolerated.

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“…The Radiation Therapy Oncology Group (RTOG) performed a phase III study of hyperbaric oxygen for patients with advanced cervical carcinoma. 1 The objective of the study was to determine if hyperbaric oxygen during external radiotherapy improved local control and survival compared to air breathing during external radiotherapy. Between 1972 and 1975, a total of 65 patients with stages IIB, III, and IVA cervical cancer were randomized to one of the two treatment arms.…”

Section: Hyperbaric Oxygenmentioning

confidence: 99%

Modification of the Radiation Response of Patients with Carcinoma of the Uterine Cervix

Grigsby

1999

Cancer Control

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BACKGROUND: The purpose of this review is to summarize clinical trials for patients with cervical cancer treated with irradiation and modifiers of the irradiation response. METHODS: The MEDLINE database was used to identify clinical studies that evaluated modifiers of the irradiation response for patients with carcinoma of the uterine cervix from 1970 through 1998. The studies included were prospective, randomized phase III clinical trials comparing irradiation alone to irradiation plus a chemical modifier for carcinoma of the uterine cervix. RESULTS: Various chemical agents have been combined with irradiation in the treatment of patients with carcinoma of the uterine cervix. These agents include hyperbaric oxygen, hydroxyurea, nitroimidazoles, neoadjuvant chemotherapy, and concurrent chemotherapy. CONCLUSIONS: Many prospective, randomized studies evaluating the use of chemical agents to modify the irradiation response in patients with carcinoma of the uterine cervix indicate no improvement over radiation therapy alone. However, the February 1999 NCI clinical announcement describes a survival advantage for cisplatin-based therapy and concurrent irradiation.

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Hyperbaric oxygen therapy for carcinoma of the cervix—Stages IIB, IIIA, IIIB and IVA: Results of a randomized study by the radiation therapy oncology group

Cited by 46 publications

References 8 publications

RSR13, an allosteric effector of haemoglobin, and carbogen radiosensitize FSAII and SCCVII tumours in C3H mice

RSR13, an allosteric effector of haemoglobin, and carbogen radiosensitize FSAII and SCCVII tumours in C3H mice

The efficacy of concurrent cisplatin and 5-flurouracil chemotherapy and radiation therapy for locally advanced cancer of the uterine cervix

Modification of the Radiation Response of Patients with Carcinoma of the Uterine Cervix

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