Rationale for chemoradiotherapy

Nishimura, Yasumasa

doi:10.1007/s10147-004-0443-z

Cited by 65 publications

(39 citation statements)

References 33 publications

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“…Unlike the radiation dosing schedules used in clinical practice, weekly and twice weekly schedules of X-ray irradiation were employed in this study to avoid damage in tumor-bearing mice due to frequent X-ray treatment; therefore, it would likely be difficult to observe an obvious sensitizing effect of CDDP to X-ray irradiation. ONCOLOGY REPORTS 24: 1307-1313, 2010 Figure 3. Combined effect of X-ray irradiation and oral S-1 or bolus 5-FU against human pancreatic cancer PAN-4 xenografts in mice.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has been used with molecular targeting agents in metastatic or adjuvant settings; therefore, 5-FU- ONCOLOGY REPORTS 24: 1307-1313, 2010 Gimeracil, a component of S-1, may enhance the antitumor activity of X-ray irradiation in human cancer xenograft models in vivo (9)(10)(11)(12)(13). Despite the widespread use of 5-FU, chemoradiotherapy with 5-FU has not been used to treat advanced non small-cell lung cancer (NSCLC) because 5-FU exhibits low antitumor efficacy and is not useful as an anticancer drug for treatment of NSCLC.…”

Section: Introductionmentioning

confidence: 99%

“…hypoxic cells after drug treatment, and inhibition by anticancer drugs of the accelerated repopulation of tumor cells (31).…”

mentioning

confidence: 99%

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Gimeracil, a component of S-1, may enhance the antitumor activity of X-ray irradiation in human cancer xenograft models in vivo

Fukushima

Sakamoto²,

Sakata³

et al. 2010

Oncol Rep

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Abstract. Chemoradiotherapy is a useful treatment strategy in patients with locally advanced cancers. In particular, combination of 5-fluorouracil (5-FU) with X-ray irradiation is effective for the treatment of some types of gastrointestinal cancers. We investigated the antitumor effects of combination treatment with X-ray and S-1, a unique formulation of 5-FU, on human cancer xenografts in nude mice and compared the efficacy of this treatment to that of radiotherapy combined with cisplatin, UFT, another oral 5-FU prodrug, and intravenous 5-FU. Tumors implanted into the left hind legs of mice were treated with a dose of 2 or 5 Gy X-ray irradiation on days 1 and 8, and S-1, UFT and 5-FU were administered for 14 days. The efficacy of combined treatment with 8.3 mg/kg S-1 and 2 Gy X-ray irradiation in treating non-small cell lung cancer xenografts (Lu-99 and LC-11) was significantly higher than that of treatment with S-1 alone or 2 Gy X-ray irradiation alone, and the antitumor activity of combined treatment was similar to that of 5 Gy X-ray irradiation alone. Although 8.3 mg/kg S-1 and 17.5 mg/kg UFT had equivalent antitumor activity; the antitumor efficacy of combination treatment with S-1 and 2 Gy X-ray irradiation on LC-11 tumors was significantly higher than that of combination treatment with UFT and 2 Gy X-ray irradiation. Combination treatment with S-1 and X-ray irradiation was also more effective against pancreatic tumors than combination treatment with intravenous 5-FU and X-ray irradiation. To elucidate the reason for the increased antitumor efficacy of combination treatment with S-1 and X-ray irradiation, the antitumor effect of gimeracil, one of the components of S-1, was tested in combination with 2 Gy X-ray irradiation. These experiments demonstrated that gimeracil enhanced the efficacy of X-ray irradiation against lung as well as head and neck cancer xenografts in a dosedependent manner. Furthermore, we observed decreased expression of Á-H2AX protein, a marker of DNA repair, in LC-11 tumors treated with X-ray irradiation and gimeracil compared to that observed in tumors treated with X-ray irradiation alone, suggesting that gimeracil may inhibit rapid repair of X-ray-induced DNA damage in tumors. The present study suggests that chemoradiotherapy using S-1 acts through a novel mechanism and may prove useful in treating patients with locally advanced cancers whose disease progression is difficult to control using chemotherapy alone.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gimeracil, a component of S-1, may enhance the antitumor activity of X-ray irradiation in human cancer xenograft models in vivo

Fukushima

Sakamoto²,

Sakata³

et al. 2010

Oncol Rep

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show abstract

“…The additivity and radio-sensitization mechanisms are rarely specific to tumor cells and may also increase the biological damage to normal tissues (Nishimura, 2004). Therefore, a therapeutic benefit is only achieved if enhancement of the primary tumor control outweighs the additional normal-tissue toxicity.…”

Section: Introductionmentioning

confidence: 99%

A mathematical programming approach to the fractionation problem in chemoradiotherapy

Salari

Unkelbach

Bortfeld

2015

IIE Transactions on Healthcare Systems Engineering

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In concurrent chemoradiotherapy, chemotherapeutic agents are administered during the course of radiotherapy to enhance the primary tumor control. However, that often comes at the expense of increased risk of normal-tissue complications. The additional biological damage is mainly attributed to two mechanisms of action, which are the independent cytotoxic activity of chemotherapeutic agents and their interactive cooperation with radiation. The goal of this study is to develop a mathematical framework to obtain drug and radiation administration schedules that maximize the therapeutic gain for concurrent chemoradiotherapy. In particular, we analyze the impact of incorporating these two mechanisms into the radiation fractionation problem. Considering each mechanism individually, we first derive closed-form expressions for the optimal radiation fractionation regimen and the corresponding drug administration schedule. We next study the case in which both mechanisms are simultaneously present and develop a dynamic programming framework to determine optimal treatment regimens. Results show that those chemotherapeutic agents that interact with radiation may change optimal radiation fractionation regimens. Moreover, administration of chemotherapeutic agents possessing both mechanisms may give rise to optimal non-stationary fractionation schemes.

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“…Concurrent chemoradiotherapy has now been established as a standard treatment based on evidence of improved efficacy in treatment outcomes as compared with only radiation therapy (4)(5)(6)(7)(8). However, the response of various tumors to chemoradiotherapy can vary greatly, even for tumors of the same histologic type, for a given treatment regimen.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Time-Dependent Effects of Irradiation on Multidrug Resistance in a Non–Small Lung Cancer Cell Line

Kono

Utsunomiya

Kanno

et al. 2014

Molecular Cancer Therapeutics

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Multidrug resistance (MDR) in cancer is known to decrease the therapeutic efficacy of chemotherapy. The effects of irradiation on MDR in cancer cells remain unclear. Tc-99m methoxyisobutylisonitrile (MIBI) exhibits the same ATP-binding cassette (ABC) transporter kinetics as the chemotherapeutic compound doxorubicin. In this study, we investigated the synergistic effects of chemotherapeutics and irradiation [0 Gy: C (control) group; 3, 6, 9, 12 Gy: I (irradiation) group] in the human non-small lung cancer cell line H1299 exhibiting MDR, on MIBI and doxorubicin ABC transporter kinetics, in vitro and in vivo, respectively. In vitro, inhibition of H1299 cell proliferation by irradiation was found to be irradiation dose dependent. The degree and duration of MDR inhibition in vitro in H1299 were also dose dependent. In the cells of both the C group and 3-Gy I group, no significant difference of MIBI accumulation was observed. In the 6-Gy I group, a higher MIBI accumulation was observed at only 7 days after irradiation relative to the C group. A higher MIBI accumulation in the 9-and 12-Gy I groups with a significant difference from the C group was observed at 4 to 14 days after irradiation. A significant negative correlation between intracellular MIBI accumulation and cell replication was found. In vivo, high accumulation and retention of doxorubicin were observed in irradiated tumors in the H1299 xenograft mice group at 4 to 14 days after 9-Gy irradiation compared with the control mice group. These results provide evidence for a synergistic effect of concurrent chemotherapy and radiotherapy. Mol Cancer Ther; 13(11); 2706-12. Ó2014 AACR.

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Rationale for chemoradiotherapy

Cited by 65 publications

References 33 publications

Gimeracil, a component of S-1, may enhance the antitumor activity of X-ray irradiation in human cancer xenograft models in vivo

Gimeracil, a component of S-1, may enhance the antitumor activity of X-ray irradiation in human cancer xenograft models in vivo

A mathematical programming approach to the fractionation problem in chemoradiotherapy

Longitudinal Time-Dependent Effects of Irradiation on Multidrug Resistance in a Non–Small Lung Cancer Cell Line

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