Publicado por: sosortomolecular | 3 de Dezembro de 2013

Quimioterapia citotóxica

   Quimioterapia citotóxica aumenta a sobrevida de 5 anos no câncer sólido maligno de adultos em apenas 2,3% na Austrália e 2,1% nos Estados Unidos da América

                                                                         Graeme Morgan, Robyn Wardt e Michael Barton

                                                                                                              11-11-2013

Graeme Morgan é Diretor do Depto. de Radioterapia do Hospital Royal North Shore de Sydney, Austrália

Robyn Wardt é Diretor do Depto de Oncologia Clínica do St Vincent Hospital, Sydney, Austrália

Michael Barton Responsável pelo setor de Estatística do Serviço de Saúde de Sydney, Austrália

Tradução: José de Felippe Junior

“O mínimo impacto da quimioterapia sobre a sobrevivência entra em conflito com a percepção que muitos pacientes com câncer têm de estarem recebendo tratamento que aumentará suas chances de cura” Morgan-Wardt-Barton

“Se os pacientes soubessem quão insignificante é aumento da sobrevida com a quimioterapia, não a escolheriam”Morgan-Wardt-Barton

“Primum non nocere” Aforismo médico

“As enfermidades são muito antigas e nada a respeito delas mudou. Somos nós que mudamos ao aprender a reconhecer nelas o que antes não percebíamos” Charcot

“A verdadeira causa das doenças e a MEDICINA ainda não fizeram as pazes. É porque a MEDICINA ainda é muito jovem. E o que dizer dos tratamentos” Felippe Jr.

Em 2004, Graeme Morgan e Robyn Wardt diretores de Departamentos de Oncologia referência na Austrália e Michael Barton Diretor do Serviço de Estatística da cidade de Sidnei escreveram artigo contundente envolvendo 227.874 pacientes adultos (idade superior a 20 anos) com os 22 diferentes tipos mais frequentes de câncer (exceto leucemia) tratados na Austrália ou Estados Unidos da América em Centros de Referência que utilizaram quimioterapia citotóxica com ou sem cirurgia ou radioterapia.

A credibilidade aumenta porque os dados dos pacientes foram somente coletados de trabalhos randomizados e controlados de meta-análises ou revisões sistemáticas que reportavam sobrevida de 5 anos e ainda publicados em revistas científicas médicas de excelente nível. Muito importante é que foram afastados os pacientes que não apresentavam condições de sobreviver 5 anos, quer dizer a indicação foi curativa e não paliativa.

De uma maneira geral o estudo revelou que a adição da quimioterapia citotóxica à cirurgia ou radioterapia em 72.903 adultos com câncer tratados na Austrália aumentou a sobrevida de 5 anos em apenas 2,3% e nos 154.971 pacientes tratados nos USA em apenas 2,1%

É importante atentar que a sobrevivência de 5 anos para os pacientes diagnosticados com câncer na Austrália foi de 63,4% no período do estudo. O que estamos escrevendo aqui é a contribuição da quimioterapia no aumento da sobrevida de 5 anos.

A seguir a contribuição para o aumento da sobrevida devido à quimioterapia citotóxica em cada câncer em particular.

1-Câncer de cabeça e pescoço:

Incidência – Austrália: 2486 pts. Sobrevida de 5 anos com a QT aumenta: 2,5%

USA: 5139 pts. Sobrevida de 5 anos com a QT aumenta: 1,9%

2-Câncer de esôfago:

Incidência – Austrália: 1003 pts. Sobrevida de 2 anos com a QT aumenta: 4,8%

USA: 1521 pts. Sobrevida de 2 anos com a QT aumenta: 4,9%

3-Câncer de estomago:

Incidência – Austrália: 1904 pts. Sobrevida de 3 anos com a QT aumenta : 0,7%

USA: 3001 pts. Sobrevida de 3 anos com a QT aumenta : 0,7%

4-Câncer de colon:

Incidência – Austrália: 7243 pts. Sobrevida de 5 anos com a QT aumenta: 1,8%

USA: 13.936 pts. Sobrevida de 5 anos com a QT aumenta: 1,0%

5-Câncer de reto:

Incidência – Austrália: 4036 pts. Sobrevida de 5 anos com a QT aumenta: 5,4%

USA: 5533 pts. Sobrevida de 5 anos com a QT aumenta: 3,4%

6-Câncer de pâncreas:

Incidência – Austrália: 1728 pts. Sobrevida de 2anos com a QT aumenta: 5,6%

USA: 3567 pts. Sobrevida de 2anos com a QT aumenta: 5,6%

 7-Câncer de pulmão (não oat cell):

Incidência- Austrália: 7792 pts. Sobrevida de 5 anos com a QT aumenta: 5%

USA: 20.741 pts. Sobrevida de 5 anos com a QT aumenta: 5%

8-Sarcoma de partes moles:

Incidência- Austrália: 665 pts. Não há evidências que a quimioterapia melhore a sobrevida de 5 anos

USA: 858 pts. Não há evidências que a quimioterapia melhore a sobrevida de 5 anos

9-Melanoma maligno:

Incidência- Austrália: 7811 pts. Não há evidências que a quimioterapia melhore a sobrevida de 5 anos

USA: 8646 pts. Não há evidências que a quimioterapia melhore a sobrevida de 5 anos

 10-Câncer de mama:

Incidência – Austrália: 10.661pts. Sobrevida de 5 anos com a QT aumenta: 1,5%

USA: 31.133 pts. Sobrevida de 5 anos com a QT aumenta: 1,4%

11- Câncer uterino:

Incidência- Austrália: 1399pts. Não há evidências que a quimioterapia melhore a sobrevida de 5 anos

USA: 4611 pts. Não há evidências que a quimioterapia melhore a sobrevida de 5 anos

12-Câncer de cervix:

Incidência- Austrália: 867 pts. Sobrevida de 5 anos com a quimioterapia aumenta:12%

USA: 1825 pts. Sobrevida de 5 anos com a quimioterapia aumenta:12%

13-Câncer de ovário:

Incidência – Austrália: 1207 pts. Sobrevida de 5 anos com a QT aumenta : 8,7%

USA: 3032 pts. Sobrevida de 5 anos com a QT aumenta :  8,9%

14-Câncer de próstata:

Incidência – Austrália: 9869 pts. Não há evidências que a QT aumente a sobrevida de 5 anos

USA: 23.242 pts. Não há evidências que a QT aumente a sobrevida de 5 anos

15-Câncer de rim:

Incidência – Austrália: 2176 pts.. Não há evidências que a QT aumente a sobrevida de 5 anos

USA: 3722 pts.. Não há evidências que a QT aumente a sobrevida de 5 anos

16- Câncer de local primário desconhecido:

Incidência – Austrália: 3161 pts. Não há evidências que a QT aumente a sobrevida de 5 anos

USA: 6200 pts. Não há evidências que a QT aumente a sobrevida de 5 anos

17-Câncer de cérebro:

Incidência – Austrália: 1116 pts. Sobrevida de 5 anos com a QT aumenta : 4,9%

USA: 1824 pts. Sobrevida de 5 anos com a QT aumenta 3,7%

18-Doença de Hodgkin:

Incidência – Austrália: 341 pts.. Sobrevida de 5 anos com a QT aumenta: 35,8%

USA: 846 pts.. Sobrevida de 5 anos com a QT aumenta :40,3%

19-Linfoma não Hodgkin:

Incidência – Austrália: 3145 pts.. Sobrevida de 5 anos com a QT aumenta: 10,5%

USA: 6217 pts.. Sobrevida de 5 anos com a QT aumenta: 10,5%

20- Mieloma múltiplo:

Incidência – Austrália: 1023 pts.. Não há evidência que a QT aumente a sobrevida de 5 anos

USA: 1721 pts.. Não há evidência que a QT aumente a sobrevida de 5 anos

21- Câncer de bexiga:

Incidência – Austrália: 2802 pts..Não há evidências que a QT aumente a sobrevida de 5 anos.

USA: 6667 pts.. Não há evidências que a QT aumente a sobrevida de 5 anos.

22- Câncer de testículo: Tipo seminoma

Incidência – Austrália: 529 pts. Sobrevida de 5 anos aumenta 41,8%

USA: 989 pts. Sobrevida de 5 anos aumenta 41,8%

Discussão

Autores sérios e sem conflito de interesse, isto é, aqueles que não recebem proventos da Indústria Farmacêutica afirmam que as drogas quimioterápicas geralmente estão  desenhadas no velho conceito de “combater o DNA” . Assim sendo nos últimos 60 anos persiste o velho modo de tratar o câncer atacando o DNA e deste modo invariavelmente os tratamentos do câncer continuam a fracassar. (Gajate-2002, Bhujwalla-2001 in Gillies-2001).

Outros autores do mesmo grau de seriedade e independentes afirmam que os quimioterápicos são geralmente responsáveis por exacerbar o fenótipo maligno por induzir a parada da apoptose e desta maneira facilitar a progressão do câncer (Torigoe-2002 , Rockwell-2001).

Neste trabalho os autores mostraram em quase 250 mil pacientes que os 5 cânceres mais “quimiosensíveis”, como testículo, cervix, ovário, Doença de Hodgkin e linfoma não Hodgkin são os responsáveis apenas por 8,4% do total dos cânceres diagnosticados nos adultos com idade superior a 20 anos. A grande maioria dos cânceres dos adultos (91,6%) são pouco responsivos à quimioterapia citotóxica, porque o aumento da sobrevida de 5 anos com estes medicamentos aumentam a sobrevida em média de apenas 2,2% . Isto significa que a quimioterapia citotóxica não está sendo eficaz na imensa maioria dos tumores sólidos de adultos. É porque os pacientes continuam a procurar a quimioterapia? . Nas palavras dos autores “falta de informação”, pois, é quase certeza que “se os pacientes soubessem quão insignificante é o aumento da sobrevida com a quimioterapia, não a escolheriam”.

Os 5 cânceres mais comuns em adultos, colo-retal,mama,próstata, melanoma e pulmão são os responsáveis por 56,6% do total de cânceres diagnosticados e neste grupo a taxa de sobrevida por 5 anos devido somente à quimioterapia citotóxica foi de apenas 1,6%.

O mínimo impacto sobre a sobrevida dos cânceres mais comuns conflita com a percepção de muitos pacientes que sentem estar recebendo um tratamento que aumentará significantemente suas chances de cura. Em parte, isto reflete a apresentação dos resultados como “redução no risco” mais do que um benefício absoluto na sobrevivência e por exagerarem as respostas daqueles com “doença estável”.

O médico quimioterapeuta apresenta os resultados de um tratamento novo dizendo: “com este tratamento conseguimos aumentar o dobro na sobrevivência”. Ele somente explica os dados relativos, não os concretos. Na verdade uma eficácia de 1% que passa para 2% é o dobro da eficácia aritmeticamente.

Apesar das drogas novas e ditas melhores, das diversas combinações e a adição de novos agentes continua a baixa eficácia da quimioterapia e continuam os efeitos colaterais que diminuem a qualidade de vida: neutropenia com sepse, enjôo, vômitos, diminuição do apetite, fraqueza geral, nefrotoxicidade, cardiotoxicidade, neurotoxicidade, diminuição da cognição, etc…

Apesar da baixa eficácia no aumento da sobrevida os quimioterapeutas prescrevem um segundo, um terceiro, um quarto conjunto de drogas citotóxicas, quando as respostas são mínimas ou a doença é progressiva.

Em vista do mínimo impacto da quimioterapia citotóxica na sobrevida de 5 anos, e a falta de progressos sólidos nos últimos 20 anos, conclui-se que a principal indicação da quimioterapia seja para tratamento paliativo e não curativo.  

Vamos escrever mais uma vez: É importante atentar que a sobrevivência de 5 anos para os pacientes diagnosticados com câncer na Austrália gira ao redor de 63,4%. O que estamos escrevendo aqui é a contribuição da quimioterapia citotóxica no aumento da sobrevida de 5 anos que nos adultos australianos é de apenas 2,3%.

Conclusão

Urge o encontro de novas modalidades terapêuticas.

Referências bibliográficas:

1- Bhujwalla Z.M., Artemov D., Abooagye E., Ackerstaff E., Gillies R.J., Natarajan K., Solaiyappan M., The physiological environ-ment in cancer vascularization, invasion and metastasis, in: R.J. Gillies (Ed), The Tumor Microenvironment: Causes and Consequences of Hypoxia and Acidity, Novartis Found. Symp., vol. 240, John Wiley and Sons, Chichester, NY, pp. 23-38; 2001

2- Gajate C., Mollinedo F., Biological activities, mechanisms of action and biomedical prospect of the antitumor ether phospholipid ET-18-OCH3 (Edelfosine), a proapoptotic agent in tumor cells, Curr. Drug Metab. 3 491-525; 2002.

3- Morgan G, Wardt R & Barton MThe contribution of cytotoxic chemotherapy to 5-year survival in adult malignances. Clinical Oncology (2004) 16:549-560.

Neste trabalho encontramos 110 referências bibliográficas.

4- Rockwell S., Yuan J., Peretz S., Glazer P.M., Genomic instability in cancer, in: R. Gillies (Ed.), The tumor Microenvironment: Causes and Consequences of Hypoxia and Acidity, Novartis Found. Symp., vol 240, John Wiley and Sons, Chichester, NY, pp. 133-142; 2001.

5- Torigoe T., Izumi H., Ise T., Murakami T., Uramoto H., Ishiguchi H., Yoshida Y., Tanabe M., Nomoto M., Kohno K., Vacuolar H+ -ATPase: functional mechanisms and potential as a target for cancer chemotherapy, anti-cancer Drugs 13 237-243; 2002.


Responses

  1. Imperato et al., ( 6 ) definen como largo tiempo de supervivencia a los pacientes con glioblastoma multiforme y astrocitoma anaplásico que viven al menos 100 % más que la supervivencia promedio de los controles históricos. Es decir, 2 años para los pacientes con glioblastoma multiforme y 4 años para los pacientes con astrocitoma anaplásico. Betty en 1964 ( 7 ) señaló como el mayor tiempo de supervivencia de un paciente con glioma anaplásico, 3 años y 6 meses. En la serie de Roth y Elvidge ( 8 ) el 5 % de los pacientes con glioblastoma multiforme sobrevivieron 3 años y aproximadamente el 3 % vivió 5 años. Tatter et al., ( 1 ) en 1996 reportaron que menos del 5 % de los pacientes con glioblastoma multiforme tienen una larga sobrevida y Bhagwati ( 9 ) en 1997 planteó que el promedio de vida para un paciente con un glioma anaplásico es de 18 a 24 meses y para el glioblastoma multiforme entre 9 – 12 meses, pudiendo muy pocos pacientes sobrevivir más de 3 – 5 años después de tratamiento multidisciplinario.

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