Phase II Clinical Trial of Chemotherapy-Naïve Patients ≥ 70 Years of Age Treated With Erlotinib for Advanced Non–Small-Cell Lung Cancer

Jackman, David M.; Yeap, Beow Y.; Lindeman, Neal I.; Fidias, P.; Rabin, Michael S.; Temel, Jennifer S.; Skarin, Arthur T.; Meyerson, Matthew; Holmes, Amie L.; Borrás, Ana M.; Freidlin, Boris; Ostler, Patricia; Lucca, Joan; Lynch, Thomas J.; Johnson, Bruce E.; Jänne, Pasi A.

doi:10.1200/jco.2006.07.5754

Cited by 278 publications

(172 citation statements)

References 33 publications

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“…However, since the occurrence of skin rash is associated with the response rates and survival duration [1,41], discontinuance of the drug is unbeneficial for the treatment of cancers. Thus, role of dermatologists is important to control skin rash tolerated, as long as the rash does not reach grade 3 (severe or medically significant but not immediately lifethreatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL).…”

Section: Resultsmentioning

confidence: 99%

Erlotinib-induced Adverse Skin Reactions

Yamamoto¹

2013

TOALLJ

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Abstract:Erlotinib is low molecular-weight quinazolin derivatives which selectively inhibit the epidermal growth factor receptor (EGF-R) tyrosine kinase activity of the intracellular domain, block autophosphorylation and the subsequent signaling cascades. EGF-R is expressed on basal keratinocytes, sebocytes, the outer root sheath of hairs, and endothelial cells in the skin, and plays important roles in the regulation of differentiation, proliferation, apoptosis, attachment and migration of keratinocytes, inflammation, and wound healing. Therefore, inhibition of EGF-R causes a number of cutaneous adverse reactions. Among them, severe skin lesions are very stressful, and impair quality of life of patients. Moreover, they even bring disadvantages such as drug withdrawal or interruption. Several review papers describe representative or common skin lesions which appear either during the first a few weeks or at later phases. Common skin manifestations include papular and pustular follicular eruptions (acneiform eruption), xerosis, paronychia, pruritus, and abnormalities of hairs; however, other than those eruptions, several unusual lesions are also induced. Early intervention of dermatologists and management of skin lesions are quite important, because discontinuance of the drug is unfavorable for patients with clinical benefits for cancers. In this brief review, various cutaneous manifestations seen in Japanese patients treated with erlotinib (Tarceva) are shown, and current management of representative severe conditions is also described.

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Section: Resultsmentioning

confidence: 99%

Erlotinib-induced Adverse Skin Reactions

Yamamoto¹

2013

TOALLJ

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“…reported that a 73-year-old male squamous cell carcinoma patient with the exon 21 L858R received erlotinib and showed SD. (39) The patient's PFS from the initiation of erlotinib was 3.4 months. Rosell et al reported 19 large-cell carcinoma patients harboring exon 19 deletions or exon 21 L858R EGFR mutations received erlotinib, and the hazard ratio of the PFS was 1.15 in comparison with 176 adenocarcinoma patients harboring the exon 19 deletion or exon 21 L858R EGFR mutations.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of gefitinib for non‐adenocarcinoma non‐small‐cell lung cancer patients harboring epidermal growth factor receptor mutations: A pooled analysis of published reports

et al. 2011

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The efficacy of gefitinib for patients with non-adenocarcinoma non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is unclear, because only a small percentage of patients enrolled in the clinical trials to evaluate the efficacy of gefitinib for tumors harboring EGFR mutation were nonadenocarcinoma NSCLC. A pooled analysis was conducted to clarify the efficacy of gefitinib for non-adenocarcinoma NSCLC patients harboring EGFR mutations. A systematic search of the PUBMED databases was conducted to identify all clinical reports that contained advanced non-adenocarcinoma NSCLC patients harboring EGFR mutations and treated with gefitinib. The selected patients were advanced non-adenocarcinoma NSCLC patients harboring EGFR mutations who were treated with gefitinib and described in reports containing the data of the histology, status of EGFR mutations and response to gefitinib. This study selected 33 patients from 15 reports. Twenty-seven and three of the 33 patients were squamous cell carcinoma and adenosquamous cell carcinoma, respectively. One patient each had large-cell carcinoma, pleomorphic carcinoma and spindle cell carcinoma. Twenty-one patients (64%) had sensitive EGFR mutations. The response rate (RR), disease control rate (DCR) and median progression-free survival (mPFS) was 27%, 67-70% and 3.0 months, respectively. These factors were statistically significantly inferior in the non-adenocarcinoma NSCLC patients harboring EGFR mutations to adenocarcinoma patients harboring EGFR mutations selected from the same published reports (RR: 27% vs 66%, P = 0.000028; DCR: 67-70% vs 92-93%, P = 0.000014; mPFS: 3.0 vs 9.4 months, P = 0.0001, respectively). Gefitinib is less effective in non-adenocarcinoma NSCLC harboring EGFR mutations than adenocarcinoma harboring EGFR mutations. (Cancer Sci 2011; 102: 1032-1037 G efitinib, one of the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI), is used for the treatment of non-small-cell lung cancer (NSCLC). Two study groups have demonstrated the presence of EGFR mutations in some NSCLC patients and reported higher response rates (RR) to gefitinib therapy among these patients.(1,2) The deletion of exon 19 and point-mutation of exon 21 from T to G at codon 858 (L858R) are the most frequently encountered EGFR mutations, accounting for 90% of all the cases.(3) Approximately 3% of the mutations occur at codon 719 resulting in the substitution of glycine to cysteine, alanine or serine (G719X). In addition, approximately 3% are in-frame insertion mutations in exon 20.(4) The RR was the highest in patients with exon 19 deletions followed by L858R and G719X (81%, 71% and 56%, respectively).(5) In contrast, there are no reports of a single patient with the exon 20 insertion mutation who responded to EGFR-TKI.(5) Clinical trials were conducted based on these findings, which showed that gefitinib is an effective treatment option for first-line treatment in NSCLC patients harboring sensitive EGFR mutations with median progressio...

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“…A recent phase 2 trial of erlotinib, an inhibitor of the epidermal growth factor receptor for elderly patients, demonstrated robust median survival for front-line therapy of advanced NSCLC. 17 Thus, individualized treatment approaches with existing agents, and continued evaluation of other novel agents, remain major goals for improving outcomes in elderly NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

Comparison of outcomes for elderly patients treated with weekly paclitaxel in combination with carboplatin versus the standard 3‐weekly paclitaxel and carboplatin for advanced nonsmall cell lung cancer

Ramalingam

Perry

Rocca

et al. 2008

Cancer

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BACKGROUND.The purpose of this study was to compare the outcomes between elderly (aged ≥70 years) patients treated with paclitaxel on a weekly basis and with carboplatin (every 4 weeks) versus the standard 3‐weekly regimen of carboplatin and paclitaxel for first‐line therapy of advanced nonsmall cell lung cancer.METHODS.Of the 444 patients enrolled, 136 (31%) were aged ≥70 years. Seventy‐two patients were randomized to the weekly schedule (paclitaxel, 100 mg/m2 weekly for 3 of 4 weeks; carboplatin, area under the curve [AUC] = 6 mg/mL·min on Day 1 every 4 weeks), and 64 patients were randomized to the standard schedule (paclitaxel, 225 mg/m2; carboplatin, AUC = 6 mg/mL·min on Day 1 every 21 days). Patients with stable disease or objective response after 4 cycles of therapy were eligible for maintenance therapy with weekly paclitaxel (70 mg/m2, 3 of 4 weeks).RESULTS.The response rate for elderly patients was 26% on the weekly regimen and 19% on the standard schedule. The median survival duration for the weekly and the standard schedules was 37 weeks and 31 weeks, respectively. The 1‐year survival rates were similar at 31% and 33%. Grade 3 to 4 anemia was more common on the weekly schedule (16% vs 6%), whereas grade 3 neuropathy was less common (5.5% vs 9.5%). Nausea and emesis were also less frequent on the weekly schedule.CONCLUSIONS.Efficacy was similar between the weekly regimen and the standard regimen of carboplatin and paclitaxel for elderly patients with advanced NSCLC and may be advantageous based on its favorable tolerability profile. Cancer 2008. © 2008 American Cancer Society.

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Phase II Clinical Trial of Chemotherapy-Naïve Patients ≥ 70 Years of Age Treated With Erlotinib for Advanced Non–Small-Cell Lung Cancer

Cited by 278 publications

References 33 publications

Erlotinib-induced Adverse Skin Reactions

Erlotinib-induced Adverse Skin Reactions

Efficacy of gefitinib for non‐adenocarcinoma non‐small‐cell lung cancer patients harboring epidermal growth factor receptor mutations: A pooled analysis of published reports

Comparison of outcomes for elderly patients treated with weekly paclitaxel in combination with carboplatin versus the standard 3‐weekly paclitaxel and carboplatin for advanced nonsmall cell lung cancer

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