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Abstract Panitumumab is a monoclonal antibody against the epidermal growth factor receptor used in metastatic colorectal cancer; in addition to tumor cells, it acts on epidermal keratinocytes and on the outer root sheath and presents skin toxicity in up to 90% of cases. A scanning electron microscope was used to examine the eyelashes and hairs of a 65-year-old patient with eyelash trichomegaly, curly hair, and paronychia undergoing treatment with panitumumab. Grooving in the hair shafts were identified, which were more evident in the eyelashes. Similar to oral epidermal growth factor inhibitors (erlotinib and gefitinib), panitumumab can cause acquired pili canaliculi.
ABSTRACT
OBJECTIVE: To establish the methods of characterizing and enriching the disulfide isoforms of panitumumab which is a human IgG2 mAb that has been used in the treatment of metastatic colorectal cancer (mCRC) and evaluate the biological activity difference among the isoforms, ie, IgG2-A, IgG2-B, and IgG2-A/B. METHODS: The disulfide isoforms of panitumumab were identified by reversed-phase chromatography. The isoform-A of panitumumab was enriched upon reduction-oxidation treatment when guanidine was added and isoform-B was enriched upon reduction-oxidation treatment without guanidine. Then the molecule structural difference of the isoform-A and isoform-B was analyzed by size-exclusion chromatography. At last, the biological activities of these isoforms were further investigated by cell-killing assay. RESULTS: The component proportions of isoform A, B and A/B in panitumumab were 38%, 32% and 30%, respectively. Under reduction-oxidation conditions, the disulfide isoforms converted to isoform-A when 0.9 mol•L-1 guanidine was used, whereas isoform-B was enriched in the absence of guanidine. And isoform-A was eluted earlier in SECHPLC, suggesting a larger apparent molecular size as compared with isoform-B. Furthermore, the in vitro biological activity measurement showed an increased activity of IgG2-A compared with IgG2-B in inhibiting the growth of DiFi cells. The IC50 s for IgG2-A and IgG2-B were 0.095 46 μg•mL-1 (95% CI 0.079 86 - 0.114 1 μg•mL-1) and 0.372 8 μg•mL-1 (95% CI 0.306 7-0.453 1 μg•mL- 1), respectively. CONCLUSION: The methods for characterizing and enriching the disulfide isoforms are established. Difference in the biological activity between isform-A and isoform-B is observed. The methods will provide technical assist to the process optimization and quality control of panitumumab.
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Objective: To compare the treatment costs of different sequences of regimens including monoclonal antibodies in metastatic colorectal cancer (CRCm) treatment for the Brazilian Supplementary Healthcare System. Methods: Sixteen scenarios were analyzed, each one comparing a sequence of bevacizumab TML plus an anti-EGFR therapy in the third?line with another sequence without bevacizumab TML (non-Bev TML) in patients with CRCm wild-type RAS. The anti-EGFRs cetuximab and panitumumabwere included. The monthly and total costs of the therapeutic sequences were compared per patient. Results: The sequences with Bev TML were cost-saving in 50% of all scenarios, and especially observed over regimens starting with cetuximab in the first-line treatment. Regarding scenarios whichthe non-Bev TML sequences were less costly, they all started with bevacizumab followed by an anti-EGFR biologic drug. Conclusion: The Bev TML regimens were cost-saving compared to scenarios of non-Bev TML which started with cetuximab, and sequential use of bevacizumab beyond progression and the addition of an anti-EGFR biologic drug in the third-line for mCRC treatment. Considering the remaining scenarios in which Bev-TML was not cost-saving, those starting with Bev presented lower costs in total. Therefore, starting a treatment with bevacizumab seems to enable a more rational management of resource usage, as well as, to allow physicians to add a biologic drug in the third-line, potentially enhancing the long term management of wild-type RAS mCRC.
Objetivo: Comparar o custo de tratamento de diferentes sequências de regimes incluindo anticorpos monoclonais no tratamento de câncer colorretal metastático (CCRm) no Sistema de Saúde Suplementar Brasileiro. Métodos: Dezesseis cenários foram analisados, cada um comparando umasequência de bevacizumabe TML (Bev TML) mais um anti-EGFR em terceira linha, com outra sequência sem bevacizumabe TML (não-Bev TML). Os anti-EGFRs cetuximabe e panitumumabe forma incluídos. Os custos mensais e totais do sequenciamento terapêutico foram comparados por pacientes. Resultados: As sequências com Bev TML trouxeram economia de recursos em 50% de todos os cenários, e especialmente comparado aos regimes iniciando com cetuximabe em primeira linha detratamento. Considerando os cenários em que os regimes não-Bev TML apresentaram menos custo, todos iniciaram o sequenciamento com bevacizumabe seguido de um medicamento biológico anti-EGFR. Conclusões: Os regimes Bev TML apresentaram economia de recursos comparado aos cenários com não-Bev TML que iniciaram com cetuximabe, apesar do uso de bevacizumabe em múltiplas linhas e da adição de medicamento biológico anti-EGFR em terceira linha no tratamento de CCRm. Considerando os demais cenários em que os regimes Bev-TML não apresentaram economia de recursos, os regimes iniciando com Bev apresentaram menor custo total. Desta maneira, iniciar o tratamento com bevacizumabe proporciona um gerenciamento mais racional de uso de recursos, assim como, permite aos médicos adicionar um medicamento biológico em terceira linha, potencialmente melhorando o manejo a longo prazo do CCRm com RAS selvagem.
Subject(s)
Humans , Colorectal Neoplasms , Health Care Costs , Supplemental HealthABSTRACT
La administración de drogas que bloquean el sistema del factor de crecimiento epidérmico y su receptor ha demostrado efectos beneficiosos en pacientes con tumores sólidos de origen epitelial. Cada día resulta más frecuente el uso de múltiples modalidades terapéuticas para combatir estos tumores, las cuales incluyen la asociación de agentes blanco y cirugía. Los agentes que actúan sobre dicho sistema pudieran causar trastornos de la cicatrización al bloquear vías del sistema que también intervienen en la cicatrización de las heridas. El objetivo de este artículo es revisar y comentar acerca del conocimiento de la relación entre el uso de las drogas anti-EGF/EGFR y los trastornos en la cicatrización de las heridas. La búsqueda bibliográfica se realizó en PubMed y Google (solo en español e inglés) y se tuvo en cuenta cualquier publicación encontrada hasta enero del 2014. Se incluyeron los anticuerpos monoclonales cetuximab, panitumumab y nimotuzumab; las pequeñas moléculas erlotinib y gefitinib y las vacunas terapéuticas contra el cáncer CIMAvax EGF y HER-1. Se hace especial énfasis en los biofarmacéuticos nimotuzumab, CIMAvax EGF y HER-1; producidos en el Centro de Inmunología Molecular, La Habana, Cuba, debido a su amplio uso en Cuba y otros países de América Latina. No se encontraron evidencias de relación entre el uso de estos productos y la aparición de trastornos en la cicatrización de las heridas. Dado que los tratamientos anti-EGF/EGFR también inhiben la proliferación celular que induce el drenaje de las heridas y la migración celular inducida por las radiaciones, se sugiere que el tratamiento anti-EGF/EGFR no debe suspenderse, ni antes ni después de la cirugía y sus posibles efectos deben ser vigilados. Obviamente, se necesitan ulteriores investigaciones por parte de los farmacólogos no clínicos y clínicos, oncólogos clínicos y cirujanos oncológicos para entender mejor los procesos fisiopatológicos de cicatrización en los cánceres de origen epitelial(AU)
The use of blocking drugs for epidermal growth factor and its receptor system has shown beneficial effects in patients with solid tumors of epithelial origin. It is increasingly common to use a multi-modal treatment approach towards solid tumors, often including the association of target agents and surgical resection. Some target agents can impair wound healing or cause increasing risk of perioperative complications if they block system pathways that may intervene in wound healing. The objective of this paper was to review and comment on the existing knowledge about the relationship between the use of anti-EGF/EGFR drugs and the disorders in wound healing. Citations from PubMed and Google (English and Spanish languages only) regardless of the date of publication were reviewed to identify potentially useful articles until January 2014. Monoclonal antibodies cetuximab, panitumumab, nimotuzumab; the small molecules erlotinib and gefitinib, and the therapeutic cancer vaccines called CIMAvax EGF and HER-1. Special emphasis was made on biopharmaceuticals nimotuzumab, CIMAvax EGF and HER-1, all of them produced at the Center of Molecular Immunology, Havana, Cuba, because of their extensive use in Cuba and many Latin-American countries. No evidence of association between the use of these products and the occurrence of complications in wound healing was found. Given that the anti-EGF/EGFR treatments also inhibit the tumor cell proliferation that wound drainage induces and the radiation-induced cell migration, it is suggested that that the administration of this kind of drugs should be kept before and after the surgery and consequently, its possible effects must be under surveillance. Obviously, non-clinical and clinical pharmacologists, clinical oncologists and surgeons need further researches for better understanding the pathophysiological wound healing processes in epithelial cancers(AU)
Subject(s)
Humans , Male , Female , Wound Healing , Cancer Vaccines/therapeutic use , Antibodies, Monoclonal/immunology , Neoplasms/surgery , CubaABSTRACT
Now the targeted therapeutic drugs have become the hottest field in many kinds of cancer and appear to have the advantages of low toxicity and high efficiency. There are a lot of clinical trials on the efficiency and the side effects. This article focuses on the latest advances of the targeted drugs on digestive tract cancers.