Fractionated dose of cisplatin (CDDP) and vinorelbine (VNB) chemotherapy for elderly patients with advanced non-small cell lung cancer: Phase II trial

Buffoni, L; Dongiovanni, Diego; Barone, C.; Fissore, C.; Ottaviani, Davide; Dongiovanni, Vincenzo; Grillo, R.; Salvadori, Angelica; Birocco, Nadia; Schena, Marina; Bertetto, Oscar

doi:10.1016/j.lungcan.2006.08.013

Cited by 10 publications

(6 citation statements)

References 18 publications

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“…In the present work, we build off our previously developed self-calibrated spatial hybrid model [19] to explore the effects of DNA damaging drug dosing schedule (MTD, metronomic, fractionated) on the development of chemoresistance in simulated tumor micrometastases. We show that in the case of strongly acquired resistance, micrometastases which, with high probability, become resistant to a metronomic chemotherapy can actually be eradicated with high probability by a small number of fractionated-dose (FD) protocols [5], most of which include off-days in the later half of the week. A subset of these FD protocols are also at least as effective as MC at eradicating weakly resistant (whether acquired or pre-existing) micrometastases, which are defined as those that can be eradicated by metronomic therapy.…”

Section: Summary Of Current Workmentioning

confidence: 99%

Limiting the Development of Anti-Cancer Drug Resistance in a Spatial Model of Micrometastases

Shah

Rejniak

Gevertz

2016

Preprint

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While chemoresistance in primary tumors is well-studied, much less is known about the influence of systemic chemotherapy on the development of drug resistance at metastatic sites. In this work, we use a hybrid spatial model of tumor response to a DNA damaging drug to study how the development of chemoresistance in micrometastases depends on the drug dosing schedule. We separately consider cell populations that harbor pre-existing resistance to the drug, and those that acquire resistance during the course of treatment. For each of these independent scenarios, we consider one hypothetical cell line that is responsive to metronomic chemotherapy, and another that with high probability cannot be eradicated by a metronomic protocol. Motivated by experimental work on ovarian cancer xenografts, we consider all possible combinations of a one week treatment protocol, repeated for three weeks, and constrained by the total weekly drug dose. Simulations reveal a small number of fractionated-dose protocols that are at least as effective as metronomic therapy in eradicating micrometastases with acquired resistance (weak or strong), while also being at least as effective on those that harbor weakly pre-existing resistant cells. Given the responsiveness of very different theoretical cell lines to these few fractionated-dose protocols, these may represent more effective ways to schedule chemotherapy with the goal of limiting metastatic tumor progression.

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Section: Summary Of Current Workmentioning

confidence: 99%

Limiting the Development of Anti-Cancer Drug Resistance in a Spatial Model of Micrometastases

Shah

Rejniak

Gevertz

2016

Preprint

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“…The link between chemotherapy and neutropenia was emphasized by Buffoni et al (2006) who looked at the effect and toxicity of chemotherapeutic drugs on 30 non-small lung cancer patients treated with a combination of cisplatin and vinorelbine on day 1 and day 8 and repeated every 21 days. The major toxic effect associated with these chemotherapies was neutropenia 3 and 4 (63%).…”

Section: Chemotherapymentioning

confidence: 99%

“…The treatment also caused three deaths, two of which were due to febrile neutropenia. Hence it can be concluded that even though the combination of cisplatin and vinorelbine was very effective in the treatment of lung cancer, it was also associated with neutropenia, some of which was fatal [24]. Yamanaka et al (2007) conducted a study 1055 patients in Japan with advanced gastric cancer on oral fluoropyrimidine derivatives (S-1).…”

Section: Chemotherapymentioning

confidence: 99%

A Close Look at Neutropenia among Cancer Patients — Risk Factor and Management

Hassan¹,

Yusoff²,

Othman³

2015

Updates on Cancer Treatment

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“…At least three phase Ⅱ trials tested cisplatin/vinorelbine schedule with similar ORR and MST [39][40][41] . Both combinations demonstrated to be safe.…”

Section: Platinum-based Chemotherapy: Prospectives Studiesmentioning

confidence: 99%

“…Regarding toxicity, grade 3-4 neutropenia and thrombocytopenia were 54.3% and 6.3% for doublet respect to 14.3% and 1% for single agent. Considering non-hematological toxicity, neuropathy resulted significantly more frequent in the doubletarm 1 Mattioli et al [39] CDDP + VNR 25 mg/m 2 , weekly > 65 36 36% 11 Pereira et al [40] CDDP + VNR 60-90 mg/m² > 70 44 50% 7.5 Buffoni et al [41] CDDP + VNR 30 mg/m², day 1 and 8 ≥ 70 30 33% 7.4 Lippe et al [35] CDDP [55] . The ARIES trial evaluated bevacizumab in clinical practice.…”

Section: Bevacizumabmentioning

confidence: 99%

Advanced non-small cell lung cancer in elderly patients: A review

Buffoni¹

2015

WJR

Self Cite

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Over 50% of patients diagnosed with non-smallcell lung cancer (NSCLC) are 65 years old while 30% exceed 70 years old. Comparing elderly patients to their younger counterpart they poorly tolerate chemotherapy due to progressive reduction of organ function and age-related co-existing pathologies. Due to this reason elderly are usually excluded from platinum-based chemotherapy, which still represent the standard of care for advanced NSCLC. In every-day practice, single-agent schedule with a third-generation drug is the recommended option for elderly patients with advanced NSCLC. A modest increase in toxicity for elderly patients has been demonstrated by subgroup analyses concluding for platinum-based combination chemotherapy being similar in young patients and fit elderly. Even though the cited evidence, feasibility of chemotherapy based on platinum remains an open question. Prospective randomised trials are warranted in order to change guide lines and give the clinicians a new therapeutic option. Recent emerging role of molecular target in selecting patients for new targeted therapies suggest dedicated trials for elderly patients. The same is for more accurate evaluation of elderly patients with increasing evidence for a comprehensive geriatric assessment as a valid tool for customized treatment in NSCLC elderly patients. Suitable evidences for the treatment of elderly patients affected by advanced NSCLC together with more appropriate and validated tools for patients selection are reviewed along the manuscript.

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Fractionated dose of cisplatin (CDDP) and vinorelbine (VNB) chemotherapy for elderly patients with advanced non-small cell lung cancer: Phase II trial

Cited by 10 publications

References 18 publications

Limiting the Development of Anti-Cancer Drug Resistance in a Spatial Model of Micrometastases

Limiting the Development of Anti-Cancer Drug Resistance in a Spatial Model of Micrometastases

A Close Look at Neutropenia among Cancer Patients — Risk Factor and Management

Advanced non-small cell lung cancer in elderly patients: A review

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