A prospective randomized phase II study comparing metronomic chemotherapy with chemotherapy (single agent cisplatin), in patients with metastatic, relapsed or inoperable squamous cell carcinoma of head and neck

Patil, Vijay; Noronha, Vanita; Joshi, Amit; Muddu, Vamshi; Dhumal, Sachin; Bhosale, Bharat; Arya, Supreeta; Juvekar, Shashikant; Banavali, Shripad; D’Cruz, Anil; Bhattacharjee, Atanu; Prabhash, Kumar

doi:10.1016/j.oraloncology.2014.12.002

Cited by 75 publications

(77 citation statements)

References 30 publications

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“…16 In a case of OBD, the widely adopted method is trinomial continual reassessment, where the highest probability of toxic effect is considered. 16 Low-dose chemotherapy drugs are more effective to suppress tumors by restraining tumor vessel growth and preventing the repair of damaged vascular endothelial cells. 17 A high-dose chemotherapy drug like Cisplatin contributes to serious side effects.…”

Section: Resultsmentioning

confidence: 99%

Time-Dependent Area under the ROC Curve for Optimum Biological Dose Detection

Bhattacharjee¹,

Patil²

2016

Turkiye Klinikleri J Biostat

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Objective: In Metronomic Chemotherapy (MC) performance of specific surrogate markers plays an important role to obtain the effective treatment. It is very difficult to detect the initial threshold value of surrogate markers to get an idea about optimum dose level of MC for long-term effective treatment. The long-term effective treatment can be obtained through controlling the surrogate markers on continues measured value into a specific range. The long-term effective treatment is defined as long-term recurrence-free survival. During the treatment initiation, many surrogate markers value changes rapidly and those values are time-dependent measurements. The specification of surrogate markers threshold value can only be obtained through the application of ROC curve (AUC), Sensitivity, and Specificity analysis. Material and Methods: The application of ROC curve to detect the timedependent continuous measurement becomes complicated. In this paper, a straightforward Survival Analysis estimator through MCMC iteration for each possible time point measurement is adopted to detect the possible threshold value of surrogate markers. Results: The surrogate markers levels on angiogenesis in Head and Neck Cancer (HNC) patients are considered. Conclusion: The threshold value of the surrogate markers is detected through the formation of ROC curve.Key Words: ROC curves; area under the curve; sensitivity; specificity; risk prediction; Kaplan-Meier estimator ÖZET Amaç: Metronomik kemoterapide (MK) belirli taşıyıcı markırların performansı etkili tedaviyi elde etmede önemli rol oynamaktadır. Uzun dönem etkili tedavi için MK'nın optimum doz düzeyi hakkında fikir edinmek için taşıyıcı markırların ilk eşik değerini tespit etmek zordur. Uzun dönem etkili tedavi, taşıyıcı markırların belirli bir değişim aralığında sürekli ölçül-müş değerini kontrol ederek elde edilebilir. Uzun dönem etkili tedavi, uzun dönem nükssüz sağkalım olarak tanımlanır. Tedavi başlangıcı boyunca, birçok taşıyıcı markır değeri hızla deği-şir ve bu değerler zamana bağlı ölçümlerdir. Taşıyıcı markırların eşik değerlerinin belirlenmesi yalnızca ROC eğrisi (AUC), duyarlılık tanımlayıcılık analiz uygulamalarıyla elde edilebilir. Gereç ve Yöntemler: Zamana bağlı sürekli ölçümleri tespit etmek için ROC eğrisinin uygulanması karmaşık hale gelir. Bu makalede, taşıyıcı markırların olası eşik değerlerini tespit etmek için her olası zamana bağlı ölçüm için MCMC iterasyonu yoluyla Sağkalım analiz tahmin edicisi kullanılmıştır. Bulgular: Baş ve boyun kanseri (BBK) hastalarında anjiyogenezde taşıyıcı markır düzeyleri dikkate alınmıştır. Sonuç: Taşıyıcı markırların eşik değeri ROC eğrisinin oluşumuyla tespit edilmiştir.Anahtar Kelimeler: ROC eğrileri; eğri altında kalan alan; duyarlılık; tanımlayıcılık; risk tahmini; Kaplan-Meier tahmincisi Turkiye Klinikleri J Biostat 2016;8(2):103-9

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Section: Resultsmentioning

confidence: 99%

Time-Dependent Area under the ROC Curve for Optimum Biological Dose Detection

Bhattacharjee¹,

Patil²

2016

Turkiye Klinikleri J Biostat

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“…Patients in the metronomic arm had a median progression-free survival of 3.67 months compared to median a progression-free survival of 2.2 months in the cisplatin arm (p = 0.014). The median OS was 8.3 months (95% CI, 222.5-275.5 days) in the metronomic arm compared to a median of 5.07 months (95% CI, 104.2-199.8 days) in the cisplatin arm (p = 0.02) [46] . Though in comparison to the EXTREME study, the OS in the chemotherapy arm is lower.…”

Section: Metronomic Chemotherapy In Oral Cancersmentioning

confidence: 91%

Preoperative Chemotherapy and Metronomic Scheduling of Chemotherapy in Locally Advanced Oral Cancers

et al. 2016

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Locally advanced oral cavity cancers are treated with a multi-modality approach. Surgery is the most efficient local modality in comparison to chemoradiation in oral cancers. Preoperative chemotherapy has failed its expectations to improve disease-free survival or overall survival in resectable oral cancers. Its use as an organ preservation tool is being studied. Induction chemotherapy followed by assessment for surgery is an appropriate option for borderline resectable or technically unresectable oral cancer. Metronomic chemotherapy is being studied as a bridge to surgery and as adjuvant chemotherapy in locally advanced oral cancers. The role of induction chemotherapy in unresectable oral cancers is unproven. Metronomic chemotherapy has shown improved progression-free survival and overall survival in oral cancers in comparison to intravenous cisplatin. A phase 3 study for confirmation of this finding has begun.

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“…Long term survival (3-5 years) is 10-30% in locally advanced disease. Efforts to improve OS have been largely disappointing, but encouraging results using MC have been reported in a palliative setting [102], and other results show an improvement in two-year DFS associated with metronomic treatment [103]. On-going trials include a comparison of standard treatment (surgical resection + radiotherapy) vs oral MC in operable AJCC Stage III and IV oral squamous cell carcinoma.…”

Section: Symposiamentioning

confidence: 99%

“…It is in this context that metronomic alternatives have been sought – using in vitro and in vivo evidence to show that the combination of low dose methotrexate and celecoxib may have efficacy, followed by encouraging signs of activity in late-stage cancer patients [105–106]. A Phase II randomised trial compared single agent cisplatin to the combination of daily celecoxib and low-dose weekly methotrexate showed that OS was significantly (P = 0.02) higher in the metronomic arm (median 249 days, 95% CI: 222.5–275.5 days) compared to the cisplatin arm (median 152 days, 95% CI: 104.2–199.8 days) [102]. However, these positive results are inferior to the results with cetuximab.…”

Section: Symposiamentioning

confidence: 99%

“…Hitesh Khatwani reported on oral MC in metastatic triple negative breast cancer [119]. Vanita Noronha discussed a prospective randomised Phase II study comparing MC versus single agent cisplatin in patients with metastatic, relapsed or inoperable squamous cell carcinoma of the head and neck [102]. Avinash Pandey discussed a retrospective study of outcomes in operable oral cavity cancer in rural India [120].…”

Section: Othermentioning

confidence: 99%

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Next generation metronomic chemotherapy—report from the Fifth Biennial International Metronomic and Anti-angiogenic Therapy Meeting, 6–8 May 2016, Mumbai

Pantziarka¹,

Hutchinson²,

André³

et al. 2016

ecancer

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The 5th Biennial Metronomic and Anti-angiogenic Therapy Meeting was held on 6th – 8th May in the Indian city of Mumbai. The meeting brought together a wide range of clinicians and researchers interested in metronomic chemotherapy, anti-angiogenics, drug repurposing and combinations thereof. Clinical experiences, including many from India, were reported and discussed in three symposia covering breast cancer, head and neck cancers and paediatrics. On the pre-clinical side research into putative mechanisms of action, and the interactions between low dose metronomic chemotherapy and angiogenesis and immune responses, were discussed in a number of presentations. Drug repurposing was discussed both in terms of clinical results, particularly with respect to angiosarcoma and high-risk neuroblastoma, and in pre-clinical settings, particularly the potential for peri-operative interventions. However, it was clear that there remain a number of key areas of challenge, particularly in terms of definitions, perceptions in the wider oncological community, mechanisms of action and predictive biomarkers. While the potential for metronomics and drug repurposing in low and middle income countries remains a key theme, it is clear that there is also considerable potential for clinically relevant improvements in patient outcomes even in high income economies.

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A prospective randomized phase II study comparing metronomic chemotherapy with chemotherapy (single agent cisplatin), in patients with metastatic, relapsed or inoperable squamous cell carcinoma of head and neck

Cited by 75 publications

References 30 publications

Time-Dependent Area under the ROC Curve for Optimum Biological Dose Detection

Time-Dependent Area under the ROC Curve for Optimum Biological Dose Detection

Preoperative Chemotherapy and Metronomic Scheduling of Chemotherapy in Locally Advanced Oral Cancers

Next generation metronomic chemotherapy—report from the Fifth Biennial International Metronomic and Anti-angiogenic Therapy Meeting, 6–8 May 2016, Mumbai

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