Concurrent tirapazamine and radiotherapy for advanced head and neck carcinomas: a phase II study

Lee, Ding‐Jen; Trotti, Andy; Spencer, Sharon A.; Rostock, Robert A.; Fisher, Cheryl; Roemeling, Reinhard von; Harvey, Elizabeth; Groves, Eric

doi:10.1016/s0360-3016(98)00310-1

Cited by 75 publications

(49 citation statements)

References 17 publications

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“…Hypoxia-targeted chemotherapy not only supplements radiation and conventional chemotherapy (which primarily attack aerobic, proliferating cells) but also often interacts in a synergistic way with them. Therefore, a therapeutic benefit has been achieved in preclinical studies with several bioreductive drugs (9,10) and, more recently in the clinic, with the lead bioreductive drug tirapazamine (TPZ) (11)(12)(13). TPZ is a benzotriazine with markedly increased cell toxicity under hypoxic conditions as verified in many tumor cell lines (14).…”

mentioning

confidence: 99%

Pretreatment 18F-FAZA PET Predicts Success of Hypoxia-Directed Radiochemotherapy Using Tirapazamine

Beck¹,

Röper²,

Carlsen³

et al. 2007

Journal of Nuclear Medicine

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mentioning

confidence: 99%

Pretreatment 18F-FAZA PET Predicts Success of Hypoxia-Directed Radiochemotherapy Using Tirapazamine

Beck¹,

Röper²,

Carlsen³

et al. 2007

Journal of Nuclear Medicine

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“…In addition, several clinical trials have demonstrated the benefit of the bioreductive alkylating agent, mitomycin C, as an adjunct to radiotherapy (7), continuous hyperfractionated accelerated radiotherapy (27), or radiochemotherapy (28) in the management of head and neck cancer. Finally, clinical studies confirm the usefulness of the bioreductive agent tirapazamine as an adjunct to radiotherapy (8) or radiochemotherapy in patients with advanced head and neck cancers (29).…”

Section: Discussionmentioning

confidence: 81%

“…For example, the hypoxia-targeted bioreductive compound mitomycin C has been employed successfully in the past as an adjuvant to radiotherapy for the treatment of head and neck cancer (6,7). Recent clinical trials of the hypoxic cytotoxin tirapazamine (3-amino-1,2,4-benzotriazine-1,4-dioxide, SR-4233, TPZ) in various combination protocols demonstrate clinical proof-of-principle that drugs that exploit hypoxia can be of clinical value (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Advantage of Combining NLCQ-1 (NSC 709257) with Radiation in Treatment of Human Head and Neck Xenografts

et al. 2007

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“…These results in a mouse model predicted well for humans and demonstrated that potentially therapeutic levels are achievable at tolerable doses. 21 We have established that the same dose can be administered after RAIT without additional toxicity (unpublished data). When therapeutic efficacy RAIT ϩ cytotoxin (day 0) were compared with RAIT ϩ cytotoxin (day 14), the latter group was significantly more effective in all 4 tumor models in which RAIT induced tumor hypoxia.…”

Section: Discussionmentioning

confidence: 87%

“…Furthermore, both cytotoxins, when administered 14 days after RAIT, resulted in comparable growth control. For example, AUC 21 for GW-39 treated with RAIT ϩ SR4233 was 18.44 Ϯ 1.97 cm 3 ⅐ time, and for RAIT ϩ NLCQ-1 was 19.4 Ϯ 5.02 (p ϭ NS). For LS174T the AUC 21 values were 2.63 Ϯ 1.17 for RAIT ϩ SR4233 vs. 3.12 Ϯ 1.00 for RAIT ϩ NLCQ-1 (p ϭ NS).…”

Section: Resultsmentioning

confidence: 98%

Optimizing the use of combined radioimmunotherapy and hypoxic cytotoxin therapy as a function of tumor hypoxia

et al. 2001

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Combined radioimmunotherapy (RAIT) and hypoxic cytotoxin therapy (SR4233 or NLCQ-1) have been evaluated with both modalities administered on the same day with only moderate improvement compared with the effects of RAIT alone. In a series of studies using oxygen electrodes, immunohistochemistry and radiotracers, we have demonstrated that RAIT induces a prolonged state of hypoxia in most tumors, without affecting the pO 2 levels in normal tissues. Using serial microelectrode measurements through subcutaneous (s.c.) GW-39 human colonic xenografts, we established that the median pO 2 was unrelated to the initial size of the tumor, over a range of sizes from 1.0 to 4.0 cm. Fourteen days after mice were given a 240-Ci dose of 131 I-MN-14 anti-carcinoembryonic antigen immunoglobulin G, their median pO 2 declined from 26.1 ؎ 9.6 mmHg to 9.8 ؎ 3.9 mmHg (p < 0.001). Using the radiotracer 3 H-MISO that accumulates in hypoxic regions, uptake in GW-39, LoVo and LS174T s.c. human colonic tumors increased 3.0-to 4.2-fold from day 14 through day 28 post-RAIT, but uptake of 3 H-MISO in CALU-3 tumors remained unchanged after RAIT. Normal tissue (liver, kidney, lung) uptake of 3 H-MISO did not exhibit significant changes. The increase in tumor hypoxia was also demonstrated visually using anti-PIMO staining of tumor sections. We postulated that sequential delivery of the 2 therapeutic agents, with the hypoxic cytotoxin given 2 weeks after RAIT when tumor pO 2 levels were at their nadir, would improve the therapeutic response above either modality alone or above the 2 agents delivered on the same day. Tumor growth was compared in mice given either RAIT or cytotoxin alone, the combined treatment on the same day or with the cytotoxin delivered 14 days after RAIT. Tumor size on day 35 for RAIT-treated and SR4233-treated GW-39 were 3.56 ؎ 0.40 and 7.98 ؎ 2.50 cm 3 . When RAIT ؉ SR4233 were delivered on the same day, tumor size dropped to 2.78 ؎ 0.80 cm 3 . If RAIT was given on day 0 and SR4233 on day 14, size further declined further to 1.74 ؎ 0.32 cm 3 (p < 0.05 compared with same day delivery). For LS174T, tumor size on day 28 for RAIT-treated and SR4233-treated tumors were 1.14 ؎ 0.36 cm 3 and 3.65 ؎ 0.78 cm 3 , respectively. When RAIT ؉ SR4233 were delivered on the same day, size was 0.51 ؎ 0.174 cm 3 . If RAIT was dosed on day 0 and SR4233 was given on day 14, tumor size was 0.13 ؎ 0.07 cm 3 (p < 0.05). Similar results were obtained for LoVo, but not for CALU-3 tumors. Another hypoxic cytotoxin, NLCQ-1, was also more efficacious 2 weeks after RAIT, compared with same-day dosing. Thus, information on tumor hypoxia after radioantibody therapy could be important for ascertaining a window of opportunity when the surviving tumor regions are most responsive to hypoxic cytotoxins.

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Concurrent tirapazamine and radiotherapy for advanced head and neck carcinomas: a phase II study

Cited by 75 publications

References 17 publications

Pretreatment 18F-FAZA PET Predicts Success of Hypoxia-Directed Radiochemotherapy Using Tirapazamine

Pretreatment 18F-FAZA PET Predicts Success of Hypoxia-Directed Radiochemotherapy Using Tirapazamine

Advantage of Combining NLCQ-1 (NSC 709257) with Radiation in Treatment of Human Head and Neck Xenografts

Optimizing the use of combined radioimmunotherapy and hypoxic cytotoxin therapy as a function of tumor hypoxia

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