The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Phase I Dose-Escalation Study of the Pan-HER Inhibitor, PF299804, in Patients with Advanced Malignant Solid Tumors
Open accessPublished version of a preprint
Abstract
Purpose: PF299804 is a potent, orally available, irreversible inhibitor of tyrosine kinase human epidermal growth factor receptors (HER) 1 (EGFR), HER2, and HER4. This first-in-human study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF299804 in patients with advanced solid malignancies. Experimental Design: PF299804 was administered once daily continuously (schedule A) and intermittently (schedule B). Dose escalation proceeded until intolerable toxicities occurred. Skin biopsies were taken predose and after 14 days of treatment to establish a pharmacokinetic/pharmacodynamic relationship. Tumor response was measured once every 2 cycles. Efficacy was correlated with tumor genotypes in non–small cell lung cancer (NSCLC) patients. Results: 121 patients were included (111 in schedule A, 10 in schedule B). The maximum tolerated dose (MTD) was 45 mg/d. Dose-limiting toxicities included stomatitis and skin toxicities. Most adverse events were mild and comprised skin toxicities, fatigue, and gastrointestinal side-effects including diarrhea, nausea, and vomiting. Pharmacokinetic analyses revealed dose-dependent increases in PF299804 exposure associated with target inhibition in skin biopsy samples. Fifty-seven patients with non–small cell lung cancer (NSCLC) were treated in this study. Four patients, all previously treated with gefitinib or erlotinib (2 with exon 19 deletions, 1 with exon 20 insertion, 1 mutational status unknown), had a partial response to PF299804. Conclusions: The MTD of PF299804 is 45 mg/d. Both continuous and intermittent treatment schedules were well tolerated, and encouraging signs of antitumor activity were observed in gefitinib/erlotinib treated NSCLC patients. Clin Cancer Res; 17(5); 1131–9. ©2011 AACR.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“By contrast, other first-, second-, and third-generation TKIs had IC50 values that were above the clinically achievable plasma concentrations previously observed in patients31,41,42,43,44,45.”
From Mechanisms and clinical activity of an EGFR and HER2 exon 20–selective kinase inhibitor in non–small cell lung cancer (2018) · cites this paper as [42]
Experimental — accuracy not yet measuredIn the citing paper
“In concordance with this, clinical testing of afatinib, neratinib, and dacomitinib achieved overall response rates of 8.7%, 9.5%, and 12%, respectively, for patients harboring EGFR or HER2 exon 20 mutations25,42,46,47.”
From Mechanisms and clinical activity of an EGFR and HER2 exon 20–selective kinase inhibitor in non–small cell lung cancer (2018) · cites this paper as [42]
In the citing paper
“Non-small cell lung cancer (NSCLC) patients with tumors harboring these mutations seldom achieve clinical responses to dacomitinib and afatinib, two covalent quinazoline-based inhibitors of EGFR or HER2, respectively.”
From Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 Inhibitors (2017) · cites this paper as [25]
In the citing paper
“Some of these patients were enrolled in clinical trials of dacomitinib treatment, and one patient with D770delinsGY showed partial response (25).”
From Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 Inhibitors (2017) · cites this paper as [25]
In the citing paper
“In the phase I study of dacomitinib, 6 patients with EGFR exon 20 insertions were treated and 1 of 6 patients had a sustained PR (25).”
From Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 Inhibitors (2017) · cites this paper as [25]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Therasse, P., Arbuck, S. G., Eisenhauer, E. A., Wanders, J., Kaplan, R. S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A. T., Christian, M. C., et al. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.205 · Cited by 15,660
EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368
Self-citationGefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma
Mok, T. S., Wu, Y.-L., Thongprasert, S., Yang, C.-H., Chu, D.-T., Saijo, N., Sunpaweravong, P., Han, B., Margono, B., Ichinose, Y., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810699 · Cited by 8,261
Untangling the ErbB signalling network
Yarden, Y., & Sliwkowski, M. X. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35052073 · Cited by 6,974
Erlotinib in Previously Treated Non–Small-Cell Lung Cancer
Shepherd, F. A., Rodrigues Pereira, J., Ciuleanu, T., Tan, E. H., Hirsh, V., Thongprasert, S., Campos, D., Maoleekoonpiroj, S., Smylie, M., Martins, R., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050753 · Cited by 5,419
Shigematsu, H., Lin, L., Takahashi, T., Nomura, M., Suzuki, M., Wistuba, I. I., Fong, K. M., Lee, H., Toyooka, S., Shimizu, N., et al. (2005) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dji055 · Cited by 2,377
Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer
Rosell, R., Moran, T., Queralt, C., Porta, R., Cardenal, F., Camps, C., Majem, M., Lopez-Vivanco, G., Isla, D., Provencio, M., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0904554 · Cited by 2,373
The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP
Yun, C.-H., Mengwasser, K. E., Toms, A. V., Woo, M. S., Greulich, H., Wong, K.-K., Meyerson, M., & Eck, M. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709662105 · Cited by 2,118
BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models
Li, D., Ambrogio, L., Shimamura, T., Kubo, S., Takahashi, M., Chirieac, L. R., Padera, R. F., Shapiro, G. I., Baum, A., Himmelsbach, F., et al. (2008) · Oncogene · doi:10.1038/onc.2008.109 · Cited by 1,447
Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib
Kwak, E. L., Sordella, R., Bell, D. W., Godin-Heymann, N., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Driscoll, D. R., Fidias, P. M., Lynch, T. J., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502860102 · Cited by 966
Intragenic ERBB2 kinase mutations in tumours
Stephens, P., Hunter, C., Bignell, G., Edkins, S., Davies, H., Teague, J., Stevens, C., O'Meara, S., Smith, R., Parker, A., et al. (2004) · Nature · doi:10.1038/431525b · Cited by 802
Engelman, J. A., Zejnullahu, K., Gale, C.-M., Lifshits, E., Gonzales, A. J., Shimamura, T., Zhao, F., Vincent, P. W., Naumov, G. N., Bradner, J. E., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1885 · Cited by 730
Self-citationEngelman, J. A., & Janne, P. A. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-2248 · Cited by 706
Self-citationFry, D. W., Bridges, A. J., Denny, W. A., Doherty, A. M., Greis, K. D., Hicks, J. L., Hook, K. E., Keller, P. R., Leopold, W. R., Loo, J. A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.20.12022 · Cited by 424
Wu, J.-Y., Wu, S.-G., Yang, C.-H., Gow, C.-H., Chang, Y.-L., Yu, C.-J., Shih, J.-Y., & Yang, P.-C. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-5123 · Cited by 319
Wong, K.-K., Fracasso, P. M., Bukowski, R. M., Lynch, T. J., Münster, P. N., Shapiro, G. I., Janne, P. A., Eder, J. P., Naughton, M. J., Ellis, M. J., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-1978 · Cited by 301
Gonzales, A. J., Hook, K. E., Althaus, I. W., Ellis, P. A., Trachet, E., Delaney, A. M., Harvey, P. J., Ellis, T. A., Amato, D. M., Nelson, J. M., et al. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-2232 · Cited by 226
A rapid and sensitive enzymatic method for epidermal growth factor receptor mutation screening
Jänne, P. A., Borras, A. M., Kuang, Y., Rogers, A. M., Joshi, V. A., Liyanage, H., Lindeman, N., Lee, J. C., Halmos, B., Maher, E. A., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2047 · Cited by 214
Self-citationErlichman, C., Hidalgo, M. M., Boni, J. P., Martins, P., Quinn, S., Zacharchuk, C., Amorusi, P., Adjei, A. A., & Rowinsky, E. K. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.01.8960 · Cited by 149
Phase 1 Clinical and Pharmacokinetics Evaluation of Oral CI-1033 in Patients with Refractory Cancer
Nemunaitis, J. J., Eiseman, I. A., Cunningham, C. C., Senzer, N. N., Williams, A., Lenehan, P. F., Olson, S. C., Bycott, P. W., Schlicht, M., Zentgraff, R., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-1950 · Cited by 84
Calvo, E., Tolcher, A. W., Hammond, L. A., Patnaik, A., Bono, J. S. D., Eiseman, I. A., Olson, S. C., Lenehan, P. F., McCreery, H., LoRusso, P. M., et al. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-1187 · Cited by 81
Wong, K., Fracasso, P. M., Bukowski, R. M., Munster, P. N., Lynch, T. J., Abbas, R., Quinn, S. E., Zacharchuk, C., & Burris, H. A. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.24.18_suppl.3018 · Cited by 57
Phase I Clinical and Pharmacodynamic Evaluation of Oral CI-1033 in Patients with Refractory Cancer
Zinner, R., Nemunaitis, J. J., Eiseman, I. A., Shin, H. J. C., Olson, S. C., Christensen, J. G., Huang, X., Lenehan, P. F., Donato, N. J., & Shin, D. M. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1958 · Cited by 28
Cited by
Sorted by citations
AZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell Lung Cancer
Jänne, P. A., Yang, J. C.-H., Kim, D.-W., Planchard, D., Ohe, Y., Ramalingam, S. S., Ahn, M.-J., Kim, S.-W., Su, W.-C., Horn, L., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1411817 · Cited by 2,116
Rociletinib in EGFR-Mutated Non–Small-Cell Lung Cancer
Sequist, L. V., Soria, J.-C., Goldman, J. W., Wakelee, H. A., Gadgeel, S. M., Varga, A., Papadimitrakopoulou, V., Solomon, B. J., Oxnard, G. R., Dziadziuszko, R., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1413654 · Cited by 665
Self-citationRare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer
Harrison, P. T., Vyse, S., & Huang, P. H. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.09.015 · Cited by 637
Yasuda, H., Kobayashi, S., & Costa, D. B. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70129-2 · Cited by 610
Arcila, M. E., Nafa, K., Chaft, J. E., Rekhtman, N., Lau, C., Reva, B. A., Zakowski, M. F., Kris, M. G., & Ladanyi, M. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-0620 · Cited by 473
Metadata
- Authors
- Jänne, P. A., Boss, D. S., Camidge, D. R., Britten, C. D., Engelman, J. A., Garon, E. B., Guo, F., Wong, S., Liang, J., Letrent, S., Millham, R., Taylor, I., Eckhardt, S. G., & Schellens, J. H. M.
- Affiliations
- Authors' Affiliations: 1Dana Farber Cancer Institute and 2Massachusetts General Hospital Cancer Center, Boston, Massachusetts; 3Netherlands Cancer Institute, Division of Clinical Pharmacology, Amsterdam, The Netherlands; 4University of Colorado, Denver, Aurora, Colorado; 5University of California Los Angeles, UCLA Medical Center, Los Angeles, California; 6Clinical Pharmacology and Pharmacometrics, Pfizer (China) Research and Development Center, Shanghai, P.R. China; 7Pfizer Oncology, New London, Connecticut; 8Clinical Development and Medical Affairs, Pfizer Oncology, San Diego, California; and 9Faculty of Pharmaceutical Sciences, Division of Drug Toxicology, University Utrecht, Utrecht, the Netherlands
- University of California, Los Angeles (US)
- Venue
- Clinical Cancer Research
- Published
- 2011-03-01
- Volume
- 17
- Issue
- 5
- Pages
- 1131-1139
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC3048920
- OpenAlex
- W2161152839
- Cited by
- 181
- References
- 23
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 6 · 2022: 12 · 2021: 13 · 2020: 10 · 2019: 10 · 2018: 14 · 2017: 12 · 2016: 14 · 2015: 18 · 2014: 18 · 2013: 22 · 2012: 18
- FWCI
- 17.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Pfizer
- National Institutes of Health
- National Cancer Institute (P50CA090578, R01CA135257)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
- Keywords
- pan-HER inhibitor, EGFR, HER2, ErbB4, tyrosine kinase inhibitors, dose escalation, maximum tolerated dose, non-small cell lung cancer, stomatitis, skin toxicity, pharmacokinetics, pharmacodynamics, exon 19 deletion, exon 20 insertion, anticancer activity
- MeSH terms
- Erlotinib Hydrochloride, Gefitinib, Adult, Aged, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Female, Genotype, Heptanoic Acids, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Protein-Tyrosine Kinases, Pyrazoles, Quinazolines, Biomarkers, Tumor, Signal Transduction, Treatment Outcome, Erb-b2 Receptor Tyrosine Kinases, Maximum Tolerated Dose, ErbB Receptors, Receptor, ErbB-4
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
