Ifosfamide in Non-Small Cell Lung Cancer

Boni, C.; Zanelli, Francesca

doi:10.1159/000073359

Cited by 5 publications

(4 citation statements)

References 43 publications

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“…As a single agent, it has showed a response rate of 20-25% [21]. These results are improved when it is used in combination with cisplatin and mitomycin C [22]. The MIP regimen (mitomycin, ifosfamide, cisplatin) has showed better survival and quality of life compared to no chemotherapy, in big randomized multicenter trial with more than 800 patients [23].…”

Section: Discussionmentioning

confidence: 99%

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Dose-finding study of fixed dose gemcitabine and escalating doses of ifosfamide given on days 1 and 8 in patients with advanced non-small cell lung cancer

et al. 2006

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Section: Discussionmentioning

confidence: 99%

“…The MIP regimen (mitomycin, ifosfamide, cisplatin) has showed better survival and quality of life compared to no chemotherapy, in big randomized multicenter trial with more than 800 patients [23]. Recent trials showed equal response rates and survival by using MIP or GP (gemcitabine, platinum) regimen [22,24].…”

Section: Discussionmentioning

confidence: 99%

Dose-finding study of fixed dose gemcitabine and escalating doses of ifosfamide given on days 1 and 8 in patients with advanced non-small cell lung cancer

et al. 2006

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“…However, it should be pointed out that the dose of ifosfamide recommended in the phase II part of the above study was 1.5 g/m 2 /day over days 1 + 2 [43]. An overview of recent results obtained using ifosfamide in combinations with other newer active agents in advanced NSCLC (usually three-drug regimens) indicated that the addition of ifosfamide demonstrates an improvement in RR at the 50% level with a median survival of more than 1 year [44]. …”

Section: Discussionmentioning

confidence: 99%

A Phase II Study of the Docetaxel- Ifosfamide-Carboplatin Combination in Advanced Non-Small-Cell Lung Cancer

et al. 2005

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Purpose: In the present phase II study we evaluated the docetaxel-ifosfamide-carboplatin (DICb) combination in the outpatient setting in patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Patients with advanced NSCLC (stages IIIB/IV), WHO performance status (PS) <2, and no prior chemotherapy were eligible. Chemotherapy drug doses were: docetaxel: 80 mg/m², ifosfamide: 3.5 g/m², and carboplatin at a target area under the curve of 5 (based on Calvert’s formula), all on day 1, followed by prophylactic G-CSF. Results: Fourty patients were entered and all are evaluable for response and toxicity: median age: 64 (48–72); PS: 1 (0–1); gender: 29 males/11 females; stages: IIIB: 13 (33%), IV: 27 (67%). Metastatic sites at diagnosis included: lymph nodes: 25; bone: 7; liver: 4; brain: 5; lung nodules: 13; adrenals: 6. Responses were as follows: 22/40 [55%; 95% confidence interval (CI), 54–81%] evaluable patients responded: 4 complete responses, 18 partial responses, 11 had stable disease, and 7 had progressive disease. The median response duration was 7 months (range 2–14 months), median time to progression 9 months (range 2–18 months) and median overall survival 11 months (range 3–46+ months). 1-year survival was 47.5%. Grade 3/4 toxicities included: neutropenia 28/40, with 12 developing grade 4 and 12% febrile neutropenia, thrombocytopenia grade 3: 3/40 and grade 4: 1/40, no grade 3 neuropathy, grade 1 CNS toxicity in 3, no renal toxicity, 8 grade 2 diarrhea and 4 grade 3 vomiting. Conclusion: In the present phase II study the DICb combination yielded important activity and good tolerability in advanced NSCLC.

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“…5,7 With the co-administration of mesna uroprotection, the primary dose-limiting toxicity of ifosfamide is myelosuppression. 8 To improve the selectivity of tumor cell killing and the sparing of normal tissue, prodrug forms that can be selectively activated in tumor tissue have been widely investigated. There are several mechanisms potentially exploitable for selective prodrug activation in tumors including utilizing unique aspects of tumor physiology such as selective enzyme expression, hypoxia, and low extracellular pH.…”

Section: Introductionmentioning

confidence: 99%

Comparison of hypoxia-activated prodrug evofosfamide (TH-302) and ifosfamide in preclinical non-small cell lung cancer models

Sun

Liu

Ahluwalia

et al. 2016

Cancer Biology & Therapy

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Evofosfamide (TH-302) is a hypoxia-activated prodrug of the cytotoxin bromo-isophosphoramide. In hypoxic conditions Br-IPM is released and alkylates DNA. Ifosfamide is a chloro-isophosphoramide prodrug activated by hepatic Cytochrome P450 enzymes. Both compounds are used for the treatment of cancer. Ifosfamide has been approved by the FDA while evofosfamide is currently in the late stage of clinical development. The purpose of this study is to compare efficacy and safety profile of evofosfamide and ifosfamide in preclinical non-small cell lung cancer H460 xenograft models. Immunocompetent CD-1 mice and H460 tumor-bearing immunocompromised nude mice were used to investigate the safety profile. The efficacy of evofosfamide or ifosfamide, alone, and in combination with docetaxel or sunitinib was compared in ectopic and intrapleural othortopic H460 xenograft models in animals exposed to ambient air or different oxygen concentration breathing conditions. At an equal body weight loss level, evofosfamide showed greater or comparable efficacy in both ectopic and orthotopic H460 xenograft models. Evofosfamide, but not ifosfamide, exhibited controlled oxygen concentration breathing condition-dependent antitumor activity. However, at an equal body weight loss level, ifosfamide yielded severe hematologic toxicity when compared to evofosfamide, both in monotherapy and in combination with docetaxel. At an equal hematoxicity level, evofosfamide showed superior antitumor activity. These results indicate that evofosfamide shows superior or comparable efficacy and a favorable safety profile when compared to ifosfamide in preclinical human lung carcinoma models. This finding is consistent with multiple clinical trials of evofosfamide as a single agent, or in combination therapy, which demonstrated both anti-tumor activity and safety profile without severe myelosuppression.Abbreviations: BW, body weight; Br-IPM, a brominated analog of isophosphoramide mustard; CAA, chloroacetalde-

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Ifosfamide in Non-Small Cell Lung Cancer

Cited by 5 publications

References 43 publications

Dose-finding study of fixed dose gemcitabine and escalating doses of ifosfamide given on days 1 and 8 in patients with advanced non-small cell lung cancer

Dose-finding study of fixed dose gemcitabine and escalating doses of ifosfamide given on days 1 and 8 in patients with advanced non-small cell lung cancer

A Phase II Study of the Docetaxel- Ifosfamide-Carboplatin Combination in Advanced Non-Small-Cell Lung Cancer

Comparison of hypoxia-activated prodrug evofosfamide (TH-302) and ifosfamide in preclinical non-small cell lung cancer models

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