Modest Reductions in Dose Intensity and Drug-Induced Neutropenia have No Major Impact on Survival of Patients with Non-small Cell Lung Cancer Treated with Platinum-Doublet Chemotherapy

Brunetto, André T.; Carden, Craig P.; Myerson, James S.; Faria, A.; Ashley, S.; Popat, Sanjay; O’Brien, Mary

doi:10.1097/jto.0b013e3181eba7f9

Cited by 21 publications

(19 citation statements)

References 25 publications

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“…Six studies reported RDI and overall survival in metastatic lung cancer: five in non-small cell lung cancer (NSCLC) and one in small cell lung cancer [13][14][15][16][17][18]. Of these six studies, two analyzed overall survival by RDI (Table 2) [13,18].…”

Section: Lung Cancermentioning

confidence: 97%

A review of relative dose intensity and survival in patients with metastatic solid tumors

Havrilesky

Reiner

Morrow

et al. 2015

Critical Reviews in Oncology/Hematology

114

101

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Section: Lung Cancermentioning

confidence: 97%

A review of relative dose intensity and survival in patients with metastatic solid tumors

Havrilesky

Reiner

Morrow

et al. 2015

Critical Reviews in Oncology/Hematology

114

101

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“…Several published articles have described a positive impact of chemotherapy-induced neutropenia on survival [3][4][5][6][7][8] . Conversely, other studies illustrated no effect, or an adverse impact on survival [9,10] .…”

Section: Introductionmentioning

confidence: 99%

Impact of chemotherapy-induced neutropenia on survival in patients with breast, ovarian and cervical cancer: a systematic review

Eskander

Tewari

2012

J Hemat Malig

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Background: Recent advances in chemotherapy administration, including targeted therapies and dose-dense scheduling have led to an increased incidence of neutropenia. Chemotherapy-induced neutropenia has been shown to be associated with improved treatment outcomes in various solid tumor types. We looked to summarize the relationship between chemotherapy-induced neutropenia and survival in patients with breast, ovarian and cervical cancer and describe future directions of research. Methodology/Principle findings:A comprehensive PUBMED literature search was conducted using the key words "solid tumor", "breast cancer", "ovarian cancer", "cervical cancer", "endometrial cancer", in combination with "chemotherapy", "neutropenia", "survival", "disease recurrence" and "prognosis". The search was also guided through a review of the reference lists of original and review articles. Published papers included in the review met the following criteria: patients with breast, ovarian, endometrial or cervical cancer treated with chemotherapy; prospective and retrospective studies, both randomized and cohort designs, evaluating impact of neutropenia or leukopenia on disease outcome. Eleven studies met the inclusion criteria. Sample size ranged from 103-750 subjects. The majority of included studies were conducted in breast cancer patients (7 of 11). No studies related to endometrial cancer were identified. Outcome measures included overall survival, progression free survival and distant disease free survival. All studies were retrospective in nature. Of the 11 identified studies, 9 suggested that the occurrence of chemotherapy-induced neutropenia was associated with improvement in oncologic outcome.Conclusions/Significance: Evaluation of the impact of chemotherapy-induced neutropenia on outcomes in patients with breast, ovarian and cervical cancer is warranted utilizing prospectively collected data from patients enrolled in clinical trials.

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“…A correlation has been noted between dose intensity and efficacy in some clinical trials (22,23). However, in ovarian cancer and non-small cell lung cancer, dose modifications of specific treatments had no impact on clinical outcomes (24,25). A post hoc analysis of a phase II trial of nab-P monotherapy in metastatic breast cancer also revealed no association of dose reduction with OS (26).…”

Section: Introductionmentioning

confidence: 99%

Dose modification and efficacy of nab-paclitaxel plus gemcitabine vs. gemcitabine for patients with metastatic pancreatic cancer: phase III MPACT trial

Scheithauer¹,

Ramanathan

Moore³

et al. 2016

J. Gastrointest. Oncol.

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Background: Dose modifications following adverse events (AEs) are an important part of the management of patients with pancreatic cancer treated with chemotherapy. While dose modifications are utilized to ensure patient safety, the subsequent influence of dose adjustments on treatment exposure and efficacy have not been reported in detail. This exploratory analysis examined the influence of dose modifications on treatment exposure and efficacy in the phase III MPACT trial, which demonstrated superior efficacy of nab-paclitaxel (nab-P) plus gemcitabine (Gem) to Gem alone for the treatment of metastatic pancreatic cancer. Methods:Patients received either nab-P 125 mg/m 2 + Gem 1,000 mg/m 2 on days 1, 8, and 15 every 4 weeks or Gem 1,000 mg/m 2 weekly for the first 7 of 8 weeks (cycle 1) and then days 1, 8, and 15 every 4 weeks (cycle ≥2). The protocol allowed up to 2 dose reductions per agent. Dose delays were also used to manage toxicities.Results: Toxicities that most commonly led to dose modifications were neutropenia, peripheral neuropathy, thrombocytopenia, and fatigue for nab-P and neutropenia, thrombocytopenia, and fatigue for Gem alone.Baseline characteristics were similar in patients with dose modifications and the intent-to-treat (ITT) population. Among the 421 treated patients in the nab-P + Gem arm, all patients initiated treatment at the per-protocol nab-P starting dose of 125 mg/m 2 ; 172 (41%) had a nab-P dose reduction, and 300 (71%) had a nab-P dose delay during the study. Most dose modifications occurred after the first 3 months (2 cycles) of treatment. The majority of patients (104/172, 60%) required only 1 nab-P dose reduction, and over half of patients (163/300) had either 1 or 2 dose delays. Patients who underwent dose modifications of nab-P had greater treatment exposure than those who did not in terms of treatment duration, number of cycles administered, and cumulative dose of nab-P delivered. Overall survival (OS) was shorter in the nab-P + Gem arm for patients who did not vs. did undergo dose reduction [median, 6.9 vs. 11.4

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Modest Reductions in Dose Intensity and Drug-Induced Neutropenia have No Major Impact on Survival of Patients with Non-small Cell Lung Cancer Treated with Platinum-Doublet Chemotherapy

Abstract: This retrospective analysis demonstrates no significant relationship between survival and dose intensity (<90%), modest dose reductions (<20%), or chemotherapy-induced neutropenia in patients receiving standard doublet platinum containing chemotherapy in NSCLC.

Cited by 21 publications

References 25 publications

A review of relative dose intensity and survival in patients with metastatic solid tumors

A review of relative dose intensity and survival in patients with metastatic solid tumors

Impact of chemotherapy-induced neutropenia on survival in patients with breast, ovarian and cervical cancer: a systematic review

Dose modification and efficacy of nab-paclitaxel plus gemcitabine vs. gemcitabine for patients with metastatic pancreatic cancer: phase III MPACT trial

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