RESUMO
This review highlights major achievements of the Russian oncology in the past decades, such as works of N.N. Petrov, L.A. Zilber, N.N. Blokhin, E.E. Pogosyants. Revolutionary shift in the understanding of the malignization process have become possible after decoding of human genome, as well as genome of several tumors such as breast cancer, acute myeloblastic leukemia, several brain tumors, testicular cancer and other neoplasms. The issue of stem cells being possible ancestors of tumor cells is also discussed in the review. Also the author observes main modern therapeutic approaches towards cancer treatment. It is specially highlighted that XXI century molecular biology achievements made it possible to start personal tumor treatment based on its' specific genotype.
Assuntos
Oncologia/história , Neoplasias/história , Antineoplásicos/história , Antineoplásicos/uso terapêutico , Tratamento Farmacológico/história , Tratamento Farmacológico/métodos , História do Século XX , História do Século XXI , Humanos , Mutação , Neoplasias/genética , Neoplasias/terapia , Federação Russa , Células-Tronco/patologiaRESUMO
BACKGROUND: This retrospective study was carried out to evaluate the prognostic significance of clinical factors in patients treated for metastatic gastric cancer with second-line chemotherapy. PATIENTS AND METHODS: We evaluated the prognostic significance of various clinical factors in 126 patients, who were treated with second-line chemotherapy. RESULTS: Median progression-free and overall survival (OS) for second-line chemotherapy were 3.3 and 5.3 months, respectively, with an overall response rate of 11.1%. Multivariate analysis identified three independent prognostic factors: performance status: Eastern Cooperative Oncology Group zero to one [hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.7-5.4], hemoglobin (Hb) level: >/=10 g/dl (HR 2.2, 95% CI 2.1-2.4) and time-to-progression (TTP) under first-line therapy: >/=5 months (HR 0.5, 95% CI 0.3-0.8). From the obtained data, a prognostic index was constructed, dividing the patients into three risk groups: good (n = 40), intermediate (n = 36) and poor risk group (n = 56). The median survival for good, intermediate and poor risk groups were 13.5, 6.0 and 2.9 months, respectively, whereas the 1-year OS rates were 50.2%, 14.2% and 2.6%, respectively (P = 0.00001). CONCLUSIONS: With inadequate data from randomized controlled trials at the moment, our report indicates that second-line chemotherapy is effective and beneficial in patients with good performance status, higher Hb level along with higher TTP under first-line therapy.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células em Anel de Sinete/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma de Células em Anel de Sinete/patologia , Cisplatino/administração & dosagem , Docetaxel , Etoposídeo/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Estadiamento de Neoplasias , Neoplasias Ovarianas/secundário , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Taxoides/administração & dosagemAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medula Óssea/efeitos dos fármacos , Hematínicos/uso terapêutico , Imidazóis/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Caproatos , Ciclofosfamida/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Doxorrubicina/efeitos adversos , Feminino , Humanos , Leucopenia/induzido quimicamente , Leucopenia/tratamento farmacológico , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Neoplasias Ovarianas/patologia , Resultado do Tratamento , GencitabinaRESUMO
5-Fluorouramcil has been the medicine of choice for systemic treatment of metastatic colonic cancer for the last 35 years. Objective positive results of this therapy were documented in 30% of the cases, it delayed the development of active disease by 4 months, and ensured a 6 month survival. Introduction of irinotecan, oxaliplatin, capecitabine, S = 1, and other drugs into clinical practice improved overall efficiency of therapy to 40-50%, increased time till progression of the disease to 6 months and survival to 15 months. Targeted drugs (bevacizumab, cetuximab) combined with the known chemotherapeutic programs (FOLFOX, FOLFIRI, XELIRI, XELFOX, etc.) showed even higher therapeutic effect, i.e. overall efficiency 50-60%, time to progression 10 months and survival of more than 1.5 years. Panitumumab is an active agent to be used in the third-line therapy.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/secundário , Humanos , Resultado do TratamentoRESUMO
Since the late 1990s, docetaxel (Dtx), an antitubular drug, has been studied as a tool for the treatment of GC. Maximum effectiveness of docetaxel as monotherapy amounted to 24%, with a median survival of 7 months. Two-drug combinations were developed containing docetaxel with 5-fluorouracil (DF) and docetaxel with cisplatin (DC). They proved effective in 43 and 33% of the cases respectively and ensured a similar median survival of 9-10 months. Clinical studies of a three-component combination containing docetaxel, 5-fluorouracil and cisplatin (DCF) as first-line therapy of metastatic GC were carried out in the XXIst century and showed its efficacy in 50% of the cases with a median survival of 10-12 months. The DCF regimen may be considered as a new standard for the treatment of patients with metastatic GC and satisfactory health status (ECOG 0-1). The combination is being modified to improve its toxicity profile by substituting oxaliplatin for cisplatin and oral fluoropyrimidines for i.v. 5-fluorouracil.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/secundário , Taxoides/uso terapêutico , Docetaxel , Humanos , Radiossensibilizantes , Resultado do TratamentoAssuntos
Antineoplásicos/efeitos adversos , Imidazóis/uso terapêutico , Leucopoese/efeitos dos fármacos , Adulto , Idoso , Caproatos , Feminino , Humanos , Imidazóis/farmacologia , Terapia de Imunossupressão , Leucopenia/induzido quimicamente , Leucopenia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/prevenção & controle , Trombocitopenia/induzido quimicamente , Trombocitopenia/prevenção & controle , Resultado do TratamentoRESUMO
Phase-I clinical studies of teraphtal and a "teraphtal + ascorbic acid" catalytic system have been completed. The dose-limiting toxicity and maximum tolerable dose were not reached even at the end of maximal dose trials. No side-effects characteristic of antitumor cytostatic drugs were registered. The gravest side-effect ever recorded was a collapse which could not be linked to teraphtal dosage and was probably caused by hypersensitivity to the drug. The drug was recommended for phase II trials.
Assuntos
Antineoplásicos/uso terapêutico , Indóis/uso terapêutico , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Feminino , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Sarcoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológicoRESUMO
This study retrospectively evaluated the influence of drug dose delivery components (DDDC) of bleomycin, etoposide and cisplatin chemotherapy for metastatic nonseminomatous germ cell tumors on treatment outcome (NSGCT). Between December 1987 and January 1995, 75 NSGCT patients were treated with a median of 4 cycles (range 3-8) of cisplatin 120 mg/m2 on day 1, etoposide 100 mg/m2 on days 1 through 5 and bleomycin 30 U on days 1, 3, and 5 every 3 weeks. DDDC, such as cumulative dose, cumulative dose in mg/m2, dose intensity (DI), relative dose intensity (RDI), dose intensity products, and relative dose intensity products by drug, were calculated and tested as possible predictors of treatment outcome in patients classified according to Indiana University (IU), and International Germ Cell Cancer Cooperative Group (IGCCCG) classifications. Overall complete response (CR) rate was 64%, and 3-year progression-free survival (PFS) was 59%. By IU classification there were statistical differences in CR and survival between moderate (89-81%) and advanced disease (42-40%) (p < 0.005), while for patients classified according to IGCCCG criteria, statistical differences in CR and PFS there were not registered. DI (mg/m2/week) and RDI values for the entire group were: cisplatin 33-0.82; etoposide 133-0.80 and bleomycin 11-0.37. We did not observe a statistically significant difference in drug dose delivery components for treatment outcome between patients who achieved a CR and incomplete response when analyzed by either extent of disease or whole group. Extent of disease was the most important predictor of treatment outcome.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Germinoma/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Biomarcadores Tumorais/sangue , Bleomicina/administração & dosagem , Gonadotropina Coriônica/sangue , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Etoposídeo/administração & dosagem , Humanos , Masculino , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Testiculares/mortalidade , Resultado do Tratamento , alfa-Fetoproteínas/análiseAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/secundário , Seminoma/tratamento farmacológico , Seminoma/patologia , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Prognóstico , Indução de Remissão , Análise de Sobrevida , Resultado do TratamentoRESUMO
The purpose of this study was to evaluate the efficacy and toxicity of paclitaxel and cisplatin combination chemotherapy as salvage treatment in patients with non-seminomatous germ cell tumour. Sixteen patients with histologically proven germ cell tumour, measurable disease and/or elevated serum tumour markers were eligible for the protocol. All patients had previously not achieved a complete remission (CR) to platinum-based induction chemotherapy and cytoreductive surgery. The treatment consisted of paclitaxel 175-225 mg/m2 as a 3-hour infusion, followed by cisplatin 100 mg/m2, repeated every 3 weeks for up to four cycles. Seven patients achieved a marker-positive partial remission (PR) by the end of the cisplatin-based induction chemotherapy; the remainder had disease progression at the start of the paclitaxel plus cisplatin treatment. One (6%) CR and 3 (19%) PRs were achieved, with an overall response rate of 25% (90% confidence interval 7-43). The duration of the CR is currently 9+ months; two PRs lasted 2 months. One patient with a PR has been lost to follow-up. During a median follow-up of 8 months (range 1-11), 12 patients died from the disease progression. The median survival for the whole group was 7 months. Toxicity was moderate, with neutropenia grade 3 occurring in 29% of patients, thrombocytopenia grade 1-3 in 29%, creatinine > 130 mmol/l in 36%, peripheral neuropathy grade 1-2 in 50%, and nausea and vomiting in 43%. Paclitaxel plus cisplatin showed modest activity, with an overall response rate of 31% in patients with poor prognosis who had not achieved a CR on induction chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Disgerminoma/tratamento farmacológico , Disgerminoma/secundário , Terapia de Salvação , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Adulto , Antineoplásicos Fitogênicos/administração & dosagem , Cisplatino/administração & dosagem , Esquema de Medicação , Humanos , Masculino , Paclitaxel/administração & dosagem , Indução de Remissão , Análise de Sobrevida , Falha de Tratamento , Resultado do TratamentoAssuntos
Glutationa Transferase/sangue , Glutationa/sangue , Melanoma/sangue , Neoplasias Ovarianas/sangue , Neoplasias Cutâneas/sangue , Neoplasias Testiculares/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Melanoma/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Propionatos/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológicoRESUMO
The treatment of advanced gastric carcinoma is a challenge to oncologists. Within the last 6-7 years several new regimens have been introduced: EAP, FAMTX, MEP, MVP, ELF. Overall response rate of these schemes is 30-40%, a complete response seldom reaching 10%. Anticancer drugs significantly improve quality of life. Chemotherapy of advanced cancer is the method of choice. New combinations and regimens may appear promising.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Quimioterapia Adjuvante , Humanos , Cuidados Pós-Operatórios , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgiaRESUMO
Efficacy and safety of toremifene 60 and 240 mg daily (TOR 60 and TOR 240) are compared to 40 mg tamoxifen daily (NFV 40) in postmenopausal women with advanced estrogen receptor (ER) positive of ER unknown breast cancer. The study is randomized in three parallel groups. Primary efficacy variables are response rate and time to progression. WHO and ECOG criteria were used for measurable and nonmeasurable disease assessment, respectively. Safely was reported according to WHO criretia. Altogether 463 patients were randomized (157 to TOR 60, 157 to TOR 240 and 149 to TAM 40). By data cut-off, after 20.5 months medianfollow-up time, over 70% of the patients had experienced disease progression. Response rates are 20.4%, 28.7% in TOR 60, TOR 240 and TAM 40, respectively. TOR 60 and TAM 40 show statistically equivalent efficacy and the difference between TOR 240 and TAM 40 is not significant (P = 0.112). Median times to progression are 4.9 (TOR 60), 6.1 (TOR 240) and 5.0 (TAM 40) months and corresponding hazard ratios (TAM:TOR) 1.015 and 1.124. Again, TOR 60 and TAM 40 are statistically equivalent and the difference between TOR 240 and TAM 40 is not significant (P = 0.374). All treatments were well tolerated. As a conclusion TOR 60 and TAM 40 show equivalent clinical efficacy and tolerability. The higher dose of toremifene slightly but not significantly improved response rate and time to progression. In postmenopausal women, toremifene (60 mg) daily is an effective and safe treatment of advanced ER positive or ER unknown breast cancer.
Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Pós-Menopausa , Tamoxifeno/administração & dosagem , Toremifeno/administração & dosagem , Idoso , Neoplasias da Mama/patologia , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
236 patients with nonseminomatous germ cell tumors have been treated for the last decade with VAB-6 combination and 188 ones with etoposide-containing regimens BEP and EP. Complete remissions were achieved in 97(41%) VAB-6 treated patients, 72(31%) patients were currently alive without evidence of the disease for 76 months of follow-up. Patients on BEP-EP presented better outcomes: 130(69%) of 188 patients achieved a complete remission and 119(63%) of them were free of symptoms within 47 months of follow-up. In spite of more pronounced toxicity, mainly myelosuppression, etoposide-containing combinations are more efficient than VAB-6 and should be considered as an induction chemotherapy in patients with nonseminomatous germ cell tumors.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Germinoma/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Clorambucila/administração & dosagem , Clorambucila/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dactinomicina/administração & dosagem , Dactinomicina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Germinoma/diagnóstico , Germinoma/mortalidade , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Indução de Remissão , Federação Russa/epidemiologia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/mortalidade , Fatores de Tempo , Vimblastina/administração & dosagem , Vimblastina/efeitos adversosRESUMO
To determine the maximum tolerated dose (MTD), and therapeutic efficacy of carboplatin (CBDCA) in combination with etoposide and bleomycin (CEB) as initial chemotherapy for poor prognosis germ cell tumors, a CBDCA dose escalation supported with GM-CSF had been performed. Twenty four untreated patients were treated with CBDCA 400 mg/m2 on day 1, etoposide 100 mg/m2 on days 1 to 5 and bleomycin 30 mg on days 1, 3, 5. Four cycles were scheduled at 21-day interval. The first cohort of 6 patients received only initial chemotherapy regimen. In the subsequent cohorts of six patients, the CBDCA dose was increased by 100 mg/m2. A fixed dose and schedule of GM-CSF at 5 micrograms/kg subcutaneously was given on days 6 through 15. Myelosuppression, with neutropenic fever and hemorrhages, was the dose-limiting toxicity at the 600 mg/m2 dose level. The recommended dose of CBDCA is 500 mg/m2. Overall complete response (CR) rate was 71% and with median follow up of 25 (16-34) months, 58% of patients are alive and have no evidence of disease (NED). A higher number of CR was achieved with CBDCA dose higher than 400 mg/m2 compared with CBDCA dose of 400 mg/m2 (92 vs. 50%, p = 0.03), as well as a higher proportion of patients who are alive and with NED (75 vs. 42%, p = 0.1). Despite GM-CSF support, the MTD of CBDCA could not be increased beyond 500 mg/m2 (50% of the dose escalation), due to severe myelosuppression. The treatment outcomes obtained with CEB in our study are no better than the standard cisplatin-based chemotherapy. Further studies of this regimen, where CBDCA dose should be calculated according to the patients glomerular filtration rate are warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Germinoma/tratamento farmacológico , Adulto , Bleomicina/administração & dosagem , Carboplatina/administração & dosagem , Etoposídeo/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Neutropenia/induzido quimicamente , Neutropenia/prevenção & controle , PrognósticoRESUMO
The increasing doses of 2.4-3.5 g/m2 ifosfamide, i/v, dropwise, were administered for 40 min, on days 1-5 each week, for 3 weeks, in 4 courses. Simultaneously, MESNA was given in a dose two-thirds of that of ifosfamide. The maximum single tolerable dose of ifosfamide was 3.2 g/m2. The dose of 3.5 g/m2 proved neurotoxic causing encephalopathy. The other toxic effects were stage III-IV neutropenia (47%), nausea and vomiting (91%) and weakness (33%). No clinical evidence of renal failure was attributed to the high dosage of the drug in the course of assays of biochemical components of the blood, blood- and urine-beta-2-microglobulins, N-acetyl-D-hexoaminidase (NAG) level in urine, creatinine clearance and complex renoscintigraphy data. On days 3-5, ifosfamide treatment was followed by increase in NAG and beta-2-microglobulin levels in urine which pointed to the toxic effect exerted on the epithelium of renal tubules. The antitumor effect was apparent in 5 (29%) patients for 6 months, which testifies to the high effectiveness of ifosfamide treatment for soft-tissue sarcoma.
Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Sarcoma/tratamento farmacológico , Adulto , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Antibióticos Antineoplásicos/efeitos adversos , Fármacos Cardiovasculares/uso terapêutico , Doxorrubicina/efeitos adversos , Insuficiência Cardíaca/prevenção & controle , Coração/efeitos dos fármacos , Razoxano/uso terapêutico , Antibióticos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antineoplásicos Alquilantes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/efeitos adversos , Coração/diagnóstico por imagem , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Ventriculografia com Radionuclídeos , Resultado do TratamentoRESUMO
The treatment of testicular cancer has undergone considerable evolution since the introduction of cisplatin and widespread recognition of its curative potentials in any stage of this disease. The authors provide a review of today's therapeutic approaches to testicular cancer with special emphasis on the disease stage and tumor histology.
Assuntos
Germinoma/terapia , Neoplasias Testiculares/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Germinoma/patologia , Humanos , Excisão de Linfonodo , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Seminoma/patologia , Seminoma/terapia , Neoplasias Testiculares/patologiaRESUMO
The treatment of testicular cancer has undergone considerable evolution since the introduction of cisplatin and widespread recognition of its curative potentials at any stages of disease. This article provides an overview on statistical and epidemiological information, the latest developments in testicular cancer biology. Also, the results of treating 360 patients with nonseminomatous and 97 patients with seminomatous germ cell tumors are presented. A combined chemotherapy with cisplatin, etoposide and bleomycin demonstrates the highest rate of activity in nonseminomatous germ cell tumor patients. Surgical resection of residual masses after chemotherapy continues to be an important component of combined modality therapy in nonseminomatous testicular tumors. The needs for regular clinical examination during a follow-up have been underlined.