Dose‐dense vinorelbine and docetaxel with Filgrastim support in patients with advanced nonsmall cell lung carcinoma

Page, Ray D.; Smith, Frederick P.; Geils, George F.; Beall, Charles L.; Fridman, Moshe; Allen, Barbara J.

doi:10.1002/cncr.21400

Cited by 10 publications

(8 citation statements)

References 113 publications

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“…The schedule variable also interacted with the ratio of docetaxel and vinorelbine, suggesting that the ratio was only important if the clinicians chose to intersperse single drug doses between treatments with the combination of drugs (test 8, Table IV). The results of the tests were similar when additional trials, mainly with paclitaxel substituted for docetaxel, were included in the dataset (57,(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77).…”

Section: Analysis Of Chemotherapy Clinical Trialsmentioning

confidence: 75%

Pattern analysis of microtubule-polymerizing and -depolymerizing agent combinations as cancer chemotherapies

Uppal

Li²,

Wendt³

et al. 2007

Int J Oncol

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Abstract. Subcellular distribution of mass can be analyzed by a technique that involves culturing cells on interferometers and digitizing their interference contours. Contour sampling resulted in 102 variables per cell, which were predictors of oncogenic transformation. Cell phenotypes can be deconstructed by use of latent factors, which represent the covariance of the real variables. The reversal of the cancertype phenotype by a combination of microtubule-stabilizing and -depolymerizing agents was described previously. The implications of these results have been explored by clinicians who treated patients with the combination of docetaxel and vinorelbine (Navelbine ® ). The current study was performed to determine the effects of different combinations on phenotype and in phases of the cell cycle other than mitosis. Combinations of paclitaxel with either colchicine, podophyllotoxin, nocodazole, or vinblastine caused phenotype reversal. Paclitaxel analogue, 7-deoxytaxol, by itself caused reversal. Factors #4, (filopodia), #5 (displacement and/or deep invaginations in the periphery), #8, and #12 took on values typical of normal cells, whereas the values of #7 (p21-activated kinase), and #13 (rounding up) shifted toward the cancer-type. All combinations altered microtubule arrangement at the cell edge. Delivery schedules and drug ratios used in clinical studies were subjected to analysis. Clinical response rates were better when the combination was not interspersed with a single agent (P=0.004). The results support the idea that efficacy depends upon simultaneous exposure to both agents, and suggest a novel mechanism for combination therapies. These therapies appear to restore in transformed cells some of the features of a contactinhibited cell, and to impede progress through the cell cycle even when provided at nanomolar concentrations.

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Section: Analysis Of Chemotherapy Clinical Trialsmentioning

confidence: 75%

Pattern analysis of microtubule-polymerizing and -depolymerizing agent combinations as cancer chemotherapies

Uppal

Li²,

Wendt³

et al. 2007

Int J Oncol

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“…We chose vinorelbine and docetaxel as the alternative regimen as it does not mechanistically overlap with the original regimen, it has an exceptionally high response rates in clinical trials in metastatic NSCLC, 20, 21 and it been tested in the adjuvant setting. 22 …”

Section: Introductionmentioning

confidence: 99%

Adaptive Neoadjuvant Chemotherapy Guided by 18 F-FDG PET in Resectable Non–Small Cell Lung Cancers: The NEOSCAN Trial

Chaft

Dunphy

Naidoo

et al. 2016

Journal of Thoracic Oncology

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Introduction Although perioperative chemotherapy improves survival in patients with resectable lung cancers, systemic recurrence remains common. Neoadjuvant chemotherapy permits response assessment and opportunity to switch treatment regimens. Response measured by fluorodeoxyglucose PET correlates better than CT with clinical outcomes. The NEOSCAN trial assessed PET-measured response rate to alternative chemotherapy in patients with a suboptimal PET response after 2 cycles of neoadjuvant chemotherapy. Methods This phase 2 study enrolled patients with resectable stage IB-IIIA lung cancers (primary tumor ≥2 cm and SUVpeak≥4.5). Patients had a pretreatment FDG PET/CT before 2 cycles of cisplatin (or carboplatin) + gemcitabine (squamous) or pemetrexed (adenocarcinomas) then repeat PET/CT. If SUVpeak in the primary tumor decreased by ≥35%, patients continued the initial chemotherapy. Individuals with <35% PET response were switched to vinorelbine + docetaxel. Post operative radiotherapy was recommended to all patients with positive N2 nodes. A Simon-optimal two stage design was used to evaluate the primary endpoint of a PERCIST-defined response rate to vinorelbine + docetaxel in previously non-responding patients. Results 40 patients were enrolled. 15 patients (38%, 95% CI: 38–53%) had <35% decrease in SUVpeak and 13 received vinorelbine + docetaxel. The study met its primary endpoint with 10/15 (67%) PET metabolic responses to alternate therapy. Chemotherapy toxicities never precluded surgical exploration. Conclusions Utilizing FDG PET/CT to assess response and change preoperative chemotherapy in non-responding patients can improve radiographic measures of response. This adaptive approach can also be used to test new drugs, attempting to optimize perioperative chemotherapy to achieve better long term outcomes.

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“…This is consistent with the findings of 2 other trials, which documented a relatively lower incidence (14%–15%) of febrile neutropenia in patients receiving docetaxel 60 mg/m 2 and vinorelbine 45 mg/m 2 in a dose-dense, every-2-week schedule supported with filgrastim (although grade 3–4 non-neutropenic infections, pulmonary toxicities, fatigue, and nausea/vomiting were frequently observed in those studies). 20,21 Hence, from a toxicity standpoint, the treatment schema used in our protocol seems tolerable and safe. Nonetheless, the requirement for filgrastim support may incur substantial inconveniences to the patients if this regimen is translated to routine clinical practice (eg, need for daily injections, possibility of bone pain, and increased costs).…”

Section: Discussionmentioning

confidence: 88%

“…Dose dense regimens, as evaluated by Miller at al. 20 and Page et al 21 as frontline treatment may represent a suitable alternative, albeit with increased incidence of side effects.…”

Section: Discussionmentioning

confidence: 99%

Phase II Study of Vinorelbine and Docetaxel in the Treatment of Advanced Non–Small-Cell Lung Cancer as Frontline and Second-Line Therapy

William¹,

Khuri²,

Fossella³

et al. 2010

American Journal of Clinical Oncology

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Objectives Combination chemotherapy with third-generation, nonplatinum agents (ie, gemcitabine, vinorelbine, taxanes, or camptothecins) represents a well-tolerated frontline treatment option for metastatic non–small-cell lung cancer and might play a role as salvage therapy as well. The aim of this phase 2 study was to investigate the use of docetaxel and vinorelbine in the frontline and second-line setting in patients with incurable non–small-cell lung cancer. Patients and Methods Seventy-eight patients (42 untreated, 36 previously treated) were administered vinorelbine (20 mg/m2) on days 1 and 8 and docetaxel (75 mg/m2 for untreated patients; 60 mg/m2 for previously treated patients for cycle 1, increased to 75 mg/m2 for the subsequent cycles in the absence of grade 3 fever/neutropenia) on day 8, repeated every 21 days, with routine filgrastim support. Results The most common grade 3 to 4 nonhematologic toxicities were diarrhea, dyspnea, fatigue, and nausea/vomiting (5% each). Grade 3 to 4 granulocytopenia occurred in 55% of the patients, however only 5% experienced febrile neutropenia. Response rates were 13% in the chemotherapy-naive cohort and 9% in previously treated patients. Median time to progression was 2.9 and 3.0 months and median overall survival was 15.0 and 6.2 months, for the frontline and second-line patients, respectively. Conclusions Compared with historical controls, in the first-line setting, the combination of docetaxel and vinorelbine did not demonstrate increased efficacy advantages over platinum- or other nonplatinum-based doublets. In the second-line setting, single agent chemotherapy is as effective as, and less toxic than the docetaxel-vinorelbine combination, and the former remains the cytotoxic treatment of choice.

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Dose‐dense vinorelbine and docetaxel with Filgrastim support in patients with advanced nonsmall cell lung carcinoma

Cited by 10 publications

References 113 publications

Pattern analysis of microtubule-polymerizing and -depolymerizing agent combinations as cancer chemotherapies

Pattern analysis of microtubule-polymerizing and -depolymerizing agent combinations as cancer chemotherapies

Adaptive Neoadjuvant Chemotherapy Guided by 18 F-FDG PET in Resectable Non–Small Cell Lung Cancers: The NEOSCAN Trial

Phase II Study of Vinorelbine and Docetaxel in the Treatment of Advanced Non–Small-Cell Lung Cancer as Frontline and Second-Line Therapy

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