Preoperative High-Dose Cisplatin Versus Moderate- Dose Cisplatin Combined with Ifosfamide and Mitomycin in Stage IIIA (N2) Non–Small-Cell Lung Cancer: Results of a Randomized Multicenter Trial

Felip, Enriqueta; Rosell, Rafael; Alberola, Vicente; Gómez-Codina, José; Maestre, José; Astudillo, J.; Camps, Carlos; Gonzalez-Larriba, J. L.; Moreno, Isabel; Paredes, Alfredo; Artal, Ángel; García-Gómez, Ramón; Garrido, Pilar; Cardenal, Felipe; Barneto, I.; Sánchez, José Javier

doi:10.3816/clc.2000.n.011

Cited by 11 publications

(8 citation statements)

References 28 publications

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“…Early trials conducted over 20 years ago showed favorable short-term results with ICTx in stage-IIIA patients; however, the benefits were insignificant with long-term follow-up in the MD Anderson study and not reproducible in the Barcelona study (6)(7)(8)(9). A 2015 meta-analysis of randomized controlled trials (RCTs) that included patients with cancers originally considered unresectable also showed no benefit to ICTx for stage-IIIA (N2) NSCLC in terms of overall survival (OS) (10).…”

Section: Introductionmentioning

confidence: 99%

Perioperative outcomes and lymph node assessment after induction therapy in patients with clinical N1 or N2 non-small cell lung cancer

et al. 2016

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Induction CTx ± RT for cN1 or cN2 NSCLC patients did not affect EBL, operative times, or in-house mortality after RAVTS lobectomy. Patients undergoing RAVTS lobectomy after ICTx+ RT may be at greater risk for RLN injury, tracheal/bronchial injury, and pulmonary embolism. Fewer N2 LN stations, but not numbers of LNs, are assessed after ICTx ± RT. Induction therapy does not lead to increased downstaging.

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Section: Introductionmentioning

confidence: 99%

Perioperative outcomes and lymph node assessment after induction therapy in patients with clinical N1 or N2 non-small cell lung cancer

et al. 2016

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“…Several clinical trials in the past have shown that the maximum tolerated dose approach has not always provide maximum clinical benefits. For example, Cisplatin, a common chemotherapy administered in non-small cell lung cancer patients, failed to show any clinical benefit in terms of overall survival or pathological complete response over relatively moderate doses in a randomized multicenter trial (27). Furthermore, retrospective analyses on low dose metronomic chemotherapy, with frequent schedules proved to be clinically favorable and safer compared to conventional chemotherapy for a large number of drugs in a broad range of tumors (28).…”

Section: Discussionmentioning

confidence: 99%

A spatial cell culture model for predicting chemotherapy dosing strategies

Zhu

Deb

Danino

2019

Preprint

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21Predicting patient responses to chemotherapy regimens is a major challenge in 22 cancer treatment. To do this requires quantitative mathematical models to predict opti-23 mal dose and frequency for a particular drug, and experimental model systems such as 24 three-dimensional organoids that accurately recapitulate the tumor microenvironment 25 and heterogeneity. However, tracking the spatial dynamics of multiple cell types in 26 three-dimensions can be a significant challenge in terms of time and throughput. Here 27we develop a two-dimensional system that allows for simple tracking of cell populations 28 via fluorescence microscopy for modeling spatial dynamics in tumors. We first develop 29 multiple 4T1 breast cancer cell lines resistant to varying concentrations of doxorubicin, 30 and demonstrate how well mixed and spatially heterogeneous populations expand in a 31 two-dimensional colony. We subject cell populations to varied dose and frequency of 32 chemotherapy and measure colony growth radius and populations. We then build a 33 mathematical model to describe the dynamics of both chemosensitive and 34 chemoresistant populations, where we determine which number of doses can produce 35 the smallest tumor size based on parameters in the system. In the future, this system 36 can be adapted to quickly optimize dosing strategies in the setting of heterogeneous cell 37 types or patient derived cells with varied chemoresistance. 38 39 Chemotherapy dosing strategies have primarily followed a maximum tolerated dosage 41 (MTD) approach, in which patients are given high doses of chemotherapy to kill as 42 many tumor cells as possible (1)(2)(3)(4)(5). This approach is based on early assumptions that 43 tumors are composed of a homogenous, exponentially growing cell population and thus 44 maximum doses are likely to cause the highest disease eradication (6, 7). However, tu-45 mors are composed of genetically heterogeneous cells with varied chemoresistance, 46 and further diversity in chemoresistance can arise due to drug selection pressure from 47

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“…8 A further example is cisplatin, where high doses have no significant clinical benefit over moderate doses in a randomized in non-small cell lung cancer. 9 Increasingly targeted drugs (e.g. palbociclib and Braf inhibitors) are being found to be as effective at lower doses or when given less frequently.…”

Section: Treatment Of Cancer (More Can Be Less)mentioning

confidence: 99%

The failure of radical treatments to cure cancer: can less deliver more?

Dalgleish

Stern

2018

Therapeutic Advances in Vaccines and Immunotherapy

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All too often attempts to deliver improved cancer cure rates by increasing the dose of a particular treatment are not successful enough to justify the accompanying increase in toxicity and reduction in quality of life suffered by a significant number of patients. In part, this drive for using higher levels of treatment derives from the nature of the process for testing and incorporation of new protocols. Indeed, new treatment regimens must now consider the key role of immunity in cancer control, a component that has been largely ignored until very recently. The recognition that some drugs developed for cytotoxicity at higher doses can display alternative anticancer activities at lower doses including through modulation of immune responses is prompting a significant re-evaluation of treatment protocol development. Given that tumours are remarkably heterogeneous and with inherent genetic instability it is probably only the adaptive immune response with its flexibility and extensive repertoire that can rise to the challenge of effecting significant control and ultimately elimination of a patient’s cancer. This article discusses some of the elements that have limited higher levels of treatment outcomes and where too much proved less effective. We explore observations that less can often be as effective, if not more effective especially with some chemotherapy regimens, and discuss how this can be exploited in combination with immunotherapies to deliver nontoxic improved tumour responses.

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Preoperative High-Dose Cisplatin Versus Moderate- Dose Cisplatin Combined with Ifosfamide and Mitomycin in Stage IIIA (N2) Non–Small-Cell Lung Cancer: Results of a Randomized Multicenter Trial

Cited by 11 publications

References 28 publications

Perioperative outcomes and lymph node assessment after induction therapy in patients with clinical N1 or N2 non-small cell lung cancer

Perioperative outcomes and lymph node assessment after induction therapy in patients with clinical N1 or N2 non-small cell lung cancer

A spatial cell culture model for predicting chemotherapy dosing strategies

The failure of radical treatments to cure cancer: can less deliver more?

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