RESUMO
Context: Bladder cancer is the fourth-most-common cancer in males in the U.S., who develop about 90% of the high-grade, carcinoma in situ (CIS) of non-muscle involved disease (NMIBC). Smoking and occupational carcinogens are well-known causes. For females without known risk factors, bladder cancer can be regarded as a sentinel environmental cancer. It's also one of the costliest to treat due to its high rate of recurrence. No treatment innovations have occurred in nearly two decades; intravesical instillation of Bacillus Calmette-Guerin (BCG), an agent in short supply globally, or Mitomycin-C (MIT-C) is effective in about 60% of cases. Cases refractory to BCG and MIT-C often undergo cystectomy, a procedure with numerous impacts on life styles and potential complications. The recent completion of a small Phase I trial of mistletoe in cancer patients that have exhausted known treatments at Johns Hopkins provides corroboration of its safety, with 25 % showing no disease progression. Objective: The study examined the benefits of pharmacologic ascorbate (PA) and mistletoe for a nonsmoking female patient with an environmental history of NMIBC refractory to BCG, in a non-smoking female with exposures in childhood and early adult life to several known carcinogens, including ultrafine particulate air pollution, benzene, toluene, and other organic solvents, aromatic amines and engine exhausts, and possibly arsenic in water. Design: The research team performed an integrative oncology case study on pharmacologic ascorbate (PA) and mistletoe, both agents shown to activate NK cells, enhance growth and maturation of T-cells, and induce dose-dependent pro-apoptotic cell death, suggesting shared and potentially synergistic mechanisms. Setting: The study began at the University of Ottawa Medical Center in Canada with treatment continuing over six years at St. Johns Hospital Center in Jackson, Wyoming, and George Washington University Medical Center for Integrative Medicine, with surgical, cytological, and pathological evaluations at University of California San Francisco Medical Center. Participant: The patient in the case study was a 76-year-old, well-nourished, athletic, nonsmoking female with high-grade CIS of the bladder. Her cancer was considered to be a sentinel environmental cancer. Intervention: Intravenous pharmacologic ascorbate (PA) and subcutaneous mistletoe (three times weekly) and intravenous and intravesical mistletoe (once weekly) were employed for an 8-week induction treatment, using a dose-escalation protocol as detailed below. Maintenance therapy was carried out with the same protocol for three weeks every three months for two years. Results: The patient has experienced a cancer-free outcome following 78 months of treatments that incorporated intravesical, intravenous, and subcutaneous mistletoe; intravenous PA; a program of selected nutraceuticals; exercise; and other supplementary treatments. Conclusions: This study is the first reported instance of combined treatments to achieve complete remission for high-grade NMIBC refractory to BCG and MIT-C, using intravesical, subcutaneous, and intravenous mistletoe and intravenous PA. It includes pharmacological information on possible mechanisms. In light of the global shortage of BCG, the high proportion of cases refractory to BCG and MIT-C, the unproven use of costly off-label pharmaceuticals, such as gemcitabine, and the relative cost-effectiveness of mistletoe and PA, clinicians should give serious consideration to employing these combined functional medicine treatments for BCG- and MIT-C-refractory NMIBC. Further research is needed with additional patients that can advance our understanding, including standardization of methods for systematically evaluating combined therapies-blinded and non-blinded, nomenclature regarding mistletoe preparation, doses, concentrations, regimes of administration, lengths of treatment, targeted cancer types, and other aspects.
Assuntos
Antineoplásicos , Carcinoma in Situ , Erva-de-Passarinho , Neoplasias da Bexiga Urinária , Humanos , Masculino , Adulto , Feminino , Idoso , Vacina BCG/uso terapêutico , Bexiga Urinária/patologia , Antineoplásicos/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Mitomicina/efeitos adversos , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/patologia , Carcinógenos , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológicoRESUMO
OBJECTIVE: To compare the safety and efficacy of 10% sinecatechins (Veregen® ) ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN). DESIGN: A Phase II double-blind randomised control trial. SETTING: A tertiary gynaecological oncology referral centre. POPULATION: All women diagnosed with primary and recurrent uVIN. METHODS: Eligible patients were randomised 1:1 to receive either sinecatechins or placebo ointment (applied three times daily for 16 weeks) and were followed up at 2, 4, 8, 16, 32 and 52 weeks. MAIN OUTCOME MEASURES: The primary outcome measure, recorded at 16 and 32 weeks, was histological response (HR). Secondary outcome measures included clinical (CR) response, toxicity, quality of life and pain scores. RESULTS: There was no observed difference in HR between the two arms. However, of the 26 patients who were randomised, all 13 patients who received sinecatechins showed either complete (n = 5) or partial (n = 8) CR, when best CR was evaluated. In placebo group, three patients had complete CR, two had partial CR, six had stable disease and two were lost to follow up. Patients in the sinecatechins group showed a statistically significant improvement in best observed CR as compared with the placebo group (P = 0.002). There was no difference in toxicity reported in either group. CONCLUSION: Although we did not observe a difference in HR between the two treatment arms, we found that 10% sinecatechins application is safe and shows promise in inducing clinical resolution of uVIN lesions and symptom improvement, thus warranting further investigation in a larger multicentre study. TWEETABLE ABSTRACT: A randomised control study indicating that sinecatechins ointment may be a novel treatment for uVIN.
Assuntos
Camellia sinensis , Carcinoma in Situ , Catequina/análogos & derivados , Neoplasias Vulvares , Adulto , Antineoplásicos/farmacologia , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/patologia , Catequina/administração & dosagem , Catequina/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Pomadas/administração & dosagem , Pomadas/efeitos adversos , Extratos Vegetais/farmacologia , Resultado do Tratamento , Neoplasias Vulvares/tratamento farmacológico , Neoplasias Vulvares/patologiaRESUMO
PURPOSE OF REVIEW: The standard diagnosis of carcinoma in situ (CIS) of the bladder, based on white light cystoscopy and urine cytology, is limited because CIS can vary from normal-appearing mucosa to a lesion indistinguishable from an inflammatory process. Intravesical instillation of Bacillus Calmette-Guerin (BCG) remains first-line therapy; however, a significant proportion of cases persist or recur after BCG treatment. This review summarizes recent improvements in the detection and treatment of CIS. RECENT FINDINGS: The new optical technologies improve CIS detection, with a potential positive impact on oncological outcomes. The usefulness of MRI-photodynamic diagnosis fusion transurethral resection in CIS detection is unclear and further studies are needed. BCG instillation remains the first-line therapy in CIS patients and seems to improve recurrence and progression rates, especially with the use of maintenance. Intravesical device-assisted therapies could be effective in both BCG-naïve and BCG-unresponsive CIS patients, but further studies are ongoing to clarify their clinical benefit. A phase II clinical trial with pembrolizumab has shown the potential effectiveness of immune checkpoint inhibitors in BCG-unresponsive CIS patients and further trials are ongoing. SUMMARY: New optical techniques increase the CIS detection rate. BCG instillation remains the first-line treatment. Immune checkpoint inhibitors could be a future alternative in BCG-naïve and BCG-unresponsive CIS patients.
Assuntos
Vacina BCG/uso terapêutico , Carcinoma in Situ/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Humanos , Recidiva Local de Neoplasia , Fotoquimioterapia , Ressecção Transuretral da PróstataRESUMO
RATIONALE: Carcinoma in situ (CIS) of the uterine cervix is a premalignant condition of squamous epithelium. The standard treatments are excision and ablation procedures; for women with positive margins, hysterectomy is recommended. PATIENT CONCERNS: A 47-year-old Peruvian woman with recurrent candidal vaginitis had been diagnosed with colpocervicitis and squamous metaplasia 8 years ago, which were not treated. DIAGNOSES: The patient was diagnosed with CIS after cervical conization procedure. She refused radical hysterectomy and opted for integrative medicine treatment. INTERVENTIONS: She was treated with intralesional and subcutaneous Viscum album L. extract (VAE) injections. VAE is a widely used herbal cancer treatment with cytotoxic, apoptogenic, and immunological effects, but it has not been investigated in cervical CIS. OUTCOMES: Ending month 5 of treatment, complete remission of cervical CIS was observed. The patient is still in remission after 30 months (until publication). LESSONS: This is the first report on complete remission of cervical CIS after intralesional and subcutaneous injection with VAE. Prospective studies should evaluate to what degree the treatment effect is reproducible.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma in Situ/tratamento farmacológico , Colo do Útero/efeitos dos fármacos , Proteínas de Plantas/administração & dosagem , Neoplasias do Colo do Útero/tratamento farmacológico , Viscum album , Feminino , Humanos , Pessoa de Meia-Idade , Indução de Remissão , Recusa do Paciente ao TratamentoRESUMO
BACKGROUND: In Belgium, bladder cancer (BC) is the fifth most common cancer in men. The per-patient lifetime cost is high. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of BC. We therefore hypothesised that selenium may be suitable for chemoprevention of recurrence of BC. METHOD: The Selenium and Bladder Cancer Trial (SELEBLAT) was an academic phase III placebo-controlled, double-blind, randomised clinical trial designed to determine the effect of selenium on recurrence of non-invasive urothelial carcinoma conducted in 14 Belgian hospitals. Patients were randomly assigned by a computer program to oral selenium yeast 200 µg once a day or placebo for three years, in addition to standard care. All study personnel and participants were blinded to treatment assignment for the duration of the study. All randomised patients were included in the intention to treat (ITT) and safety analyses. Per protocol analyses (PPAs) included all patients in the study three months after start date. RESULTS: Between September 18, 2009 and April 18, 2013, 151 and 141 patients were randomised in the selenium and placebo group. Patients were followed until December 31, 2015. The ITT analysis resulted in 43 (28%; 95% CI, 0.21-0.35) and 45 (32%; 95% CI, 0.24-0.40) recurrences in the selenium and placebo group. The hazard ratio (HR) was 0.85 (95% CI, 0.56-1.29; p = 0.44) while the HR for the PPA resulted in 42 and 39 (28%; 95% CI, 0.20-0.35) recurrences in the selenium and placebo group (HR = 0.96 [95% CI, 0.62-1.48]; p = 0.93). CONCLUSION: Selenium supplementation does not lower the probability of recurrence in BC patients.
Assuntos
Antioxidantes/uso terapêutico , Carcinoma in Situ/tratamento farmacológico , Carcinoma de Células de Transição/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Selênio/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Procedimentos Cirúrgicos Urológicos , Idoso , Idoso de 80 Anos ou mais , Bélgica , Carcinoma in Situ/patologia , Carcinoma de Células de Transição/patologia , Quimioprevenção , Quimioterapia Adjuvante , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Neoplasias da Bexiga Urinária/patologiaRESUMO
Objetivo. Analizar las recidivas de las pacientes diagnosticadas, tratadas y seguidas en nuestro centro por carcinoma ductal in situ de mama, y establecer qué variables se asocian a un mayor riesgo de desarrollarlas. Pacientes y métodos. Se ha realizado un estudio descriptivo retrospectivo de los casos de carcinoma ductal in situ diagnosticados y tratados en nuestro centro desde enero de 1999 hasta enero de 2012. Se excluyeron los casos en que coexistía componente infiltrante y aquellos con antecedente de neoplasia y/o radioterapia previa en la mama afecta. Las variables que se analizaron fueron: la edad de la paciente, el tamaño tumoral, el grado nuclear, el estado de los márgenes quirúrgicos, el tipo de cirugía y el tratamiento complementario (radioterapia y hormonoterapia). Resultados. Se estudiaron 162 casos de carcinomas in situ en el periodo 1999-2012. De estos, 117 (72,2%) fueron tratados con cirugía conservadora y 45 (27,7%) mediante mastectomía. Se produjeron 16 recidivas (9,9%) en el periodo estudiado. No se encuentran diferencias estadísticamente significativas en la tasa de recidivas en función del tamaño tumoral, la distancia quirúrgica al margen, el grado histológico ni la edad de la paciente. En el subgrupo de pacientes tratadas con tumorectomía, la supervivencia libre de enfermedad fue mayor en las que recibieron de forma complementaria radioterapia y hormonoterapia que en aquellas que solo recibieron uno o ninguno de los tratamientos (p=0,001). Conclusión. En el subgrupo de pacientes con carcinoma in situ tratadas con tumorectomía el riesgo de recidiva es 19 veces superior en los casos que no recibieron ningún tratamiento complementario que en aquellos tratados con tumorectomía, radioterapia y hormonoterapia (p=0,001) (AU)
Objective. To analyse recurrences in patients diagnosed, treated and followed up in our centre for ductal carcinoma in situ and to identify the variables associated with an increased risk of their development. Patients and methods. We performed a retrospective study of cases of ductal carcinoma in situ diagnosed and treated in our hospital from January 1999 to January 2012. We excluded cases with coexistence of an infiltrating component, a history of neoplasia, and/or prior radiation to the affected breast. The variables analysed were patient age, tumour size, nuclear grade, surgical margin status, type of surgery, and adjuvant therapy (radiation and hormone therapy). Results. We studied 162 cases of ductal carcinoma in situ occurring between 1999 and 2012. Of these, 117 cases (72.2%) were treated with conservative surgery and 45 (27.7%) by mastectomy. In that period, we found 16 recurrences (9.9%). We found no statistically significant difference in the recurrence rate according to tumour size, surgical distance from the margin, histological grade, or patient age. In the subgroup of patients treated with lumpectomy, disease-free survival was higher in patients receiving radiation therapy and hormone therapy as a complementary treatment than in those who received only one or no treatment at all (P=.001). Conclusion. In the subgroup of patients with ductal carcinoma in situ treated with lumpectomy, the recurrence risk was 19 times higher in patients who received no adjuvant treatment than in those treated with lumpectomy, radiation and hormone therapy (P=.001) (AU)
Assuntos
Humanos , Feminino , Carcinoma in Situ/epidemiologia , Carcinoma in Situ/radioterapia , Carcinoma in Situ/cirurgia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/radioterapia , Mastectomia/métodos , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/terapia , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ , Seguimentos , Estudos Retrospectivos , Hormônios/uso terapêutico , Biópsia de Linfonodo Sentinela/métodosRESUMO
The residual cancer burden index was developed as a method to quantify residual disease ranging from pathological complete response to extensive residual disease. The aim of this study was to evaluate the inter-Pathologist reproducibility in the residual cancer burden index score and category, and in their long-term prognostic utility. Pathology slides and pathology reports of 100 cases from patients treated in a randomized neoadjuvant trial were reviewed independently by five pathologists. The size of tumor bed, average percent overall tumor cellularity, average percent of the in situ cancer within the tumor bed, size of largest axillary metastasis, and number of involved nodes were assessed separately by each pathologist and residual cancer burden categories were assigned to each case following calculation of the numerical residual cancer burden index score. Inter-Pathologist agreement in the assessment of the continuous residual cancer burden score and its components and agreement in the residual cancer burden category assignments were analyzed. The overall concordance correlation coefficient for the agreement in residual cancer burden score among pathologists was 0.931 (95% confidence interval (CI) 0.908-0.949). Overall accuracy of the residual cancer burden score determination was 0.989. The kappa coefficient for overall agreement in the residual cancer burden category assignments was 0.583 (95% CI 0.539-0.626). The metastatic component of the residual cancer burden index showed stronger concordance between pathologists (overall concordance correlation coefficient=0.980; 95% CI 0.954-0.992), than the primary component (overall concordance correlation coefficient=0.795; 95% CI 0.716-0.853). At a median follow-up of 12 years residual cancer burden determined by each of the pathologists had the same prognostic accuracy for distant recurrence-free and survival (overall concordance correlation coefficient=0.995; 95% CI 0.989-0.998). Residual cancer burden assessment is highly reproducible, with reproducible long-term prognostic significance.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/patologia , Quimioterapia Adjuvante , Neoplasia Residual/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/mortalidade , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/mortalidade , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Paclitaxel/uso terapêutico , Prognóstico , Reprodutibilidade dos Testes , Taxa de Sobrevida , Carga TumoralRESUMO
PURPOSE: To report a case of ocular surface squamous neoplasia (OSSN) that resolved with topical Aloe vera eye drop treatment. METHODS: A 64-year-old Hispanic woman with a lesion typical for OSSN in her left eye was followed up with multiple clinical examinations and ocular surface photographs to document changes over time with A. vera-based topical treatment. RESULTS: The patient refused biopsy of her lesion and traditional treatments and, instead, initiated using A. vera eye drops 3 times daily. At follow-up visits, the lesion was noted to regress until it finally resolved 3 months after commencing treatment. No additional topical medications were used, and she has remained tumor free for 6 years. CONCLUSIONS: Ongoing research is warranted because A. vera may represent a new therapeutic class of medications for OSSN treatment.
Assuntos
Alantoína/uso terapêutico , Aloe/química , Antineoplásicos/uso terapêutico , Carcinoma in Situ/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Doenças da Córnea/tratamento farmacológico , Fitoterapia , Administração Tópica , Alantoína/administração & dosagem , Antineoplásicos/administração & dosagem , Carcinoma in Situ/patologia , Neoplasias da Túnica Conjuntiva/patologia , Doenças da Córnea/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Soluções Oftálmicas , Parabenos/administração & dosagem , Parabenos/uso terapêutico , Conservantes Farmacêuticos/administração & dosagem , Conservantes Farmacêuticos/uso terapêuticoRESUMO
BACKGROUND: To report rates of recurrence and complications of localized ocular surface squamous neoplasia treated with 5-fluorouracil or mitomycin C as adjunctive treatment to surgical excision. DESIGN: Long-term follow up of two prospective, non-comparative interventional case series. PARTICIPANTS: One hundred fifty-three eyes with histologically confirmed localized, non-invasive ocular surface squamous neoplasia. 89 eyes were treated with adjuvant 5-fluorouracil and 64 eyes were treated with adjuvant mitomycin C. METHODS: Following surgical excision±cryotherapy patients received topical 5-fluorouracil 1% four times daily for two weeks or topical mitomycin C 0.04% four times daily for two to three 1-week cycles. MAIN OUTCOME MEASURES: Ocular surface squamous neoplasia recurrence, complications of therapy and compliance. RESULTS: Median follow up was 33.6 (range 12-84) months and 57.9 (range 12-160) months in 5-fluorouracil and mitomycin C groups, respectively. There was one recurrence in the 5-fluorouracil group and no recurrences in the mitomycin C group. Side-effects occurred in 69% of 5-fluorouracil patients and 41% of mitomycin C patients. Five patients (6%) required intervention for treatment-related side-effects in the 5-fluorouracil group versus 11 (17%) in the mitomycin C group. No vision-threatening complications were noted. CONCLUSIONS: Long-term recurrence of localised ocular surface squamous neoplasia is rare when topical 5-fluorouracil or mitomycin C are used as adjunctive treatment to surgical excision. While side-effects are common, the majority are transient and rarely limit compliance.
Assuntos
Alquilantes/administração & dosagem , Carcinoma in Situ/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Doenças da Córnea/tratamento farmacológico , Fluoruracila/administração & dosagem , Mitomicina/administração & dosagem , Recidiva Local de Neoplasia/prevenção & controle , Administração Tópica , Idoso , Alquilantes/efeitos adversos , Carcinoma in Situ/cirurgia , Quimioterapia Adjuvante , Neoplasias da Túnica Conjuntiva/cirurgia , Doenças da Córnea/cirurgia , Crioterapia , Feminino , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/efeitos adversos , Soluções Oftálmicas , Estudos Prospectivos , Resultado do TratamentoRESUMO
Anal intra-epithelial neoplasia (AIN) is a pre-malignant condition, which over time may progress to invasive anal squamous cell carcinoma. There is no standard treatment for AIN, but one of the therapeutic options available is photodynamic therapy (PDT). There are very few published studies of the efficacy of PDT, but it has been shown to produce downgrading of high-grade dysplasia in the anal region. The aim of the study was to evaluate the role of PDT in the treatment of AIN. Fifteen patients who received anal PDT between 2004 and 2013 were identified; twelve of these had AIN, two had intra-epithelial adenocarcinoma and one had dysplasia with high-risk human papillomavirus. After a median follow-up of nineteen months, ten of these have had at least one follow-up with aceto-white staining. Six of these ten patients had a complete response to PDT, although three subsequently had some recurrence. Three further patients had a partial response to PDT. There were no major therapeutic complications. Our findings suggest that PDT is a safe and feasible treatment option for AIN, associated with reasonable response rates and relatively little morbidity. Further research into the efficacy of PDT for AIN is required.
Assuntos
Neoplasias do Ânus/terapia , Carcinoma in Situ/terapia , Fototerapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácido Aminolevulínico/uso terapêutico , Neoplasias do Ânus/tratamento farmacológico , Carcinoma in Situ/tratamento farmacológico , Éter de Diematoporfirina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Projetos PilotoRESUMO
Rose geranium (Pelargonium graveolens, Geraniaceae) has anti-cancer and anti-inflammatory properties, and promotes wound healing. Similarly, Ganoderma tsugae (Ganodermataceae), Codonopsis pilosula (Campanulaceae) and Angelica sinensis (Apiaceae) are traditional Chinese herbs associated with immunomodulatory functions. In the present study, a randomised, double-blind, placebo-controlled study was conducted to examine whether the Chinese medicinal herb complex, RG-CMH, which represents a mixture of rose geranium and extracts of G. tsugae, C. pilosula and A. sinensis, can improve the immune cell count of cancer patients receiving chemotherapy and/or radiotherapy to prevent leucopenia and immune impairment that usually occurs during cancer therapy. A total of fifty-eight breast cancer patients who received chemotherapy or radiotherapy were enrolled. Immune cell levels in patient serum were determined before, and following, 6 weeks of cancer treatment for patients receiving either an RG-CMH or a placebo. Administration of RG-CMH was associated with a significant reduction in levels of leucocytes from 31·5 % for the placebo group to 13·4 % for the RG-CMH group. Similarly, levels of neutrophils significantly decreased from 35·6 % for the placebo group to 11·0 % for the RG-CMH group. RG-CMH intervention was also associated with a decrease in levels of T cells, helper T cells, cytotoxic T cells and natural killer cells compared with the placebo group. However, these differences between the two groups were not statistically significant. In conclusion, administration of RG-CMH to patients receiving chemotherapy/radiotherapy may have the capacity to delay, or ease, the reduction in levels of leucocytes and neutrophils that are experienced by patients during cancer treatment.
Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Medicamentos de Ervas Chinesas/uso terapêutico , Imunidade Celular/efeitos dos fármacos , Leucopenia/prevenção & controle , Substâncias Protetoras/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/radioterapia , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/imunologia , Carcinoma in Situ/radioterapia , Estudos de Coortes , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Imunidade Celular/efeitos da radiação , Contagem de Leucócitos , Leucócitos/efeitos dos fármacos , Leucopenia/induzido quimicamente , Leucopoese/efeitos dos fármacos , Leucopoese/efeitos da radiação , Adesão à Medicação , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutrófilos/efeitos dos fármacos , Substâncias Protetoras/efeitos adversosRESUMO
INTRODUCTION: Photodynamic therapy (PDT) is a minimally invasive surgical intervention used in the management of tissue disorders. It can be applied before, or after, any of the conventional modalities, without compromising these treatments or being compromised itself. MATERIALS AND METHODS: In this prospective study, a total of 147 consecutive patients with oral potentially malignant disorders were treated with surface illumination PDT, using 5-ALA or mTHPC as the photosensitizer. The average age was 53 ± 8.9 years. The patients' recovery was uneventful and no complications reported. Comparisons with the clinical and histopathological features and rate of recurrence as well as malignant transformation were made. The patients were followed-up for a mean of 7.3 years. ANALYSIS AND RESULTS: Homogenous leukoplakias were identified in 55 patients, non-homogenous leukoplakias in 73 patients, whereas 19 patients had erythroplakias. Ex- and current lifelong smokers formed 84.4% of the recruited patients. While people who currently smoke and drink formed 38.1% (56 patients) of the cohort. Erythroplakias were mainly identified in heavy lifelong smokers. The most common identified primary anatomical locations were the lateral border of tongue, floor of mouth and retromolar area. Moderate dysplasia was identified in 33 patients while 63 patients had severe dysplasias; and 32 patients had a histopathological diagnosis of carcinoma in situ. The rate of recurrence in laser surgery was approximately 11.6%. Malignant transformation was observed in 11 patients (7.5%), in the tongue, floor of mouth and retromolar area. Recurrence and malignant transformation was mainly identified in erythroplakias and non-homogenous leukoplakias. The final outcome of the cohort showed that 11 (7.5%) suffered from progressive disease, 5 (3.4%) had stable disease, 12 (8.2%) were considered partially responsive to the therapy. Complete response was identified in 119/147 patients (81%). CONCLUSION: 5-ALA-PDT and/or mTHPC-PDT offer an effective alternative treatment for oral potentially malignant disorders.
Assuntos
Ácido Aminolevulínico/uso terapêutico , Leucoplasia Oral/tratamento farmacológico , Mesoporfirinas/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Idoso , Ácido Aminolevulínico/administração & dosagem , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/patologia , Carcinoma in Situ/radioterapia , Esquema de Medicação , Feminino , Humanos , Lasers Semicondutores/uso terapêutico , Leucoplasia Oral/patologia , Leucoplasia Oral/radioterapia , Terapia com Luz de Baixa Intensidade , Masculino , Mesoporfirinas/administração & dosagem , Pessoa de Meia-Idade , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The sap from Euphorbia peplus, commonly known as petty spurge in the U.K. or radium weed in Australia, has been used as a traditional treatment for a number of cancers. OBJECTIVE: To determine the effectiveness of E. peplus sap in a phase I/II clinical study for the topical treatment of basal cell carcinomas (BCC), squamous cell carcinomas (SCC) and intraepidermal carcinomas (IEC). METHODS: Thirty-six patients, who had refused, failed or were unsuitable for conventional treatment, were enrolled in a phase I/II clinical study. A total of 48 skin cancer lesions were treated topically with 100-300 µL of E. peplus sap once daily for 3 days. RESULTS: The complete clinical response rates at 1 month were 82% (n = 28) for BCC, 94% (n = 16) for IEC and 75% (n = 4) for SCC. After a mean follow-up of 15 months these rates were 57%, 75% and 50%, respectively. For superficial lesions < 16 mm, the response rates after follow-up were 100% for IEC (n = 10) and 78% for BCC (n = 9). CONCLUSIONS: The clinical responses for these relatively unfavourable lesions (43% had failed previous treatments, 35% were situated in the head and neck region and 30% were > 2 cm in diameter), are comparable with existing nonsurgical treatments. An active ingredient of E. peplus sap has been identified as ingenol mebutate (PEP005). This clinical study affirms community experience with E. peplus sap, and supports further clinical development of PEP005 for the treatment of BCC, SCC and IEC.
Assuntos
Carcinoma in Situ/tratamento farmacológico , Carcinoma Basocelular/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Euphorbiaceae , Extratos Vegetais/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/patologia , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Fitoterapia/métodos , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Bacillus Calmette-Guérin (BCG) is the intravesical treatment of choice for carcinoma in situ (CIS). OBJECTIVE: Our aim was to assess if sequential mitomycin C (MMC) plus BCG after transurethral resection (TUR) is worthy of further study in non-muscle-invasive bladder cancer patients with CIS. DESIGN, SETTING, AND PARTICIPANTS: In a noncomparative phase 2 study, 96 patients with primary/secondary/concurrent CIS of the urinary bladder were randomized to sequential MMC plus BCG or to BCG alone after TUR. INTERVENTION: Patients received six weekly instillations of MMC followed by six weekly instillations of BCG or six weekly instillations of BCG, 3 wk rest, and three further weekly instillations of BCG. Complete responders received three weekly maintenance instillations at 6, 12, 18, 24, 30, and 36 mo in accordance with the initial randomization. MEASUREMENTS: End points were complete response (CR) rate at the first control cystoscopy 16-18 wk after start of treatment, disease-free interval, overall survival, and side effects. RESULTS AND LIMITATIONS: Ninety-six patients were randomized, 48 to each treatment group. Ten patients were ineligible, and three did not start treatment. In all randomized patients, CR rates on MMC plus BCG and BCG alone were 70.8% and 66.7%, respectively. In 83 eligible patients who started treatment, CR rates were 75.6% and 73.8%, respectively. Based on a median follow-up of 4.7 yr, 25 patients (52.1%) on MMC plus BCG and 22 patients (45.8%) on BCG alone were disease free. Twelve patients stopped treatment due to toxicity: three during induction (two MMC plus BCG, one BCG) and nine during maintenance (three MMC plus BCG, six BCG). CONCLUSIONS: In the treatment of patients with CIS, sequential chemoimmunotherapy with MMC plus BCG had acceptable toxicity. CR and disease-free rates were similar to those on BCG alone and to previous publications on sequential chemoimmunotherapy. TRIAL REGISTRATION: This study was registered with the US National Cancer Institute clinical trials database (protocol ID: EORTC-30993). http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=68869&version=HealthProfessional&protocolsearchid=7920643.
Assuntos
Vacina BCG/uso terapêutico , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/cirurgia , Mitomicina/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Administração Intravesical , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/uso terapêutico , Carcinoma in Situ/mortalidade , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Análise de Sobrevida , Ressecção Transuretral da Próstata , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
BACKGROUND: Oral verrucous hyperplasia (OVH) and oral erythroleukoplakia (OEL) are two oral precancerous lesions with relatively high malignant transformation potential. One of the best cancer prevention strategies is to use a conservative and effective treatment modality to eliminate oral precancers to stop their further malignant transformation. Our previous studies have shown that the topical 5-aminolevulinic acid-mediated photodynamic therapy (topical ALA-PDT) using the 635-nm light-emitting diode (LED) light is very effective for OVH and OEL lesions. METHODS: Because the laser machine is a more-popular light source than the LED device in PDT clinics, in this study 40 OVH and 40 OEL lesions were treated once a week with the same PDT protocol but using the 635-nm laser light to evaluate whether this laser light-mediated topical ALA-PDT was also effective for OVH and OEL lesions. RESULTS: We found that all the 40 OVH lesions exhibited complete response (CR) after an average of 3.6 PDT treatments. Of the 40 OEL lesions, 38 showed CR after an average of 3.4 PDT treatments and two showed partial response (PR). Better PDT outcomes were significantly associated with OVH and OEL lesions with the smaller size, pink to red color, epithelial dysplasia, or thinner surface keratin layer. CONCLUSION: This study indicates that the laser light-mediated topical ALA-PDT is also very effective for OVH and OEL lesions. Therefore, we suggest that topical ALA-PDT using either the LED or laser light may serve as the first-line treatment of choice for OVH and OEL lesions.
Assuntos
Eritroplasia/tratamento farmacológico , Leucoplasia Oral/tratamento farmacológico , Mucosa Bucal/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Fotoquimioterapia , Lesões Pré-Cancerosas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácido Aminolevulínico/uso terapêutico , Biópsia , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/patologia , Eritroplasia/patologia , Feminino , Humanos , Hiperplasia , Queratinas/efeitos dos fármacos , Leucoplasia Oral/patologia , Terapia com Luz de Baixa Intensidade , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Fármacos Fotossensibilizantes/uso terapêutico , Lesões Pré-Cancerosas/patologia , Indução de Remissão , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the response of dysplasia, carcinoma in situ (CIS), and T1 carcinoma of the oral cavity and larynx to photodynamic therapy with porfimer sodium. DESIGN: Prospective trial. SETTING: A National Cancer Institute-designated cancer institute. PATIENTS: Patients with primary or recurrent moderate to severe oral or laryngeal dysplasia, CIS, or T1N0 carcinoma. INTERVENTION: Porfimer sodium, 2 mg/kg of body weight, was injected intravenously 48 hours before treatment. Light at 630 nm for photosensitizer activation was delivered from an argon laser or diode laser using lens or cylindrical diffuser fibers. The light dose was 50 J/cm(2) for dysplasia and CIS and 75 J/cm(2) for carcinoma. MAIN OUTCOME MEASURES: Response was evaluated at 1 week and at 1 month and then at 3-month intervals thereafter. Response options were complete (CR), partial (PR), and no (NR) response. Posttreatment biopsies were performed in all patients with persistent and recurrent visible lesions. RESULTS: Thirty patients were enrolled, and 26 were evaluable. Mean follow-up was 15 months (range, 7-52 months). Twenty-four patients had a CR, 1 had a PR, and 1 had NR. Three patients with oral dysplasia with an initial CR experienced recurrence in the treatment field. All the patients with NR, a PR, or recurrence after an initial CR underwent salvage treatment. Temporary morbidities included edema, pain, hoarseness, and skin phototoxicity. CONCLUSION: Photodynamic therapy with porfimer sodium is an effective treatment alternative, with no permanent sequelae, for oral and laryngeal dysplasia and early carcinoma. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00530088.
Assuntos
Carcinoma in Situ/tratamento farmacológico , Éter de Diematoporfirina/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Terapia com Luz de Baixa Intensidade/métodos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Lesões Pré-Cancerosas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/patologia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/patologia , Estudos Prospectivos , Resultado do TratamentoRESUMO
A single case of carcinoma in situ (actinic keratosis) was treated topically with a patch consisting of an aqueous paste of a commercially available mixture (50:1) of green tea concentrate plus Capsicum (Capsol-T®) for approximately 14 days. The carcinoma responded by the formation of apoptotic blisters whereas surrounding normal tissue showed no response. A second untreated carcinoma 17 cm distant from the treated area also responded indicative of a systemic action of the substance.
Assuntos
Camellia sinensis , Capsicum , Carcinoma in Situ/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Ceratose Actínica/tratamento farmacológico , Fitoterapia , Neoplasias Cutâneas/tratamento farmacológico , Administração Tópica , Idoso , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Humanos , Masculino , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
Reduced expression of proapoptotic and terminal differentiation genes in conjunction with increased levels of the proinflammatory and angiogenesis-inducing enzymes, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), correlate with malignant transformation of oral intraepithelial neoplasia (IEN). Accordingly, this study investigated the effects of a 10% (w/w) freeze-dried black raspberry gel on oral IEN histopathology, gene expression profiles, intraepithelial COX-2 and iNOS proteins, and microvascular densities. Our laboratories have shown that freeze-dried black raspberries possess antioxidant properties and also induce keratinocyte apoptosis and terminal differentiation. Oral IEN tissues were hemisected to provide samples for pretreatment diagnoses and establish baseline biochemical and molecular variables. Treatment of the remaining lesional tissue (0.5 g gel applied four times daily for 6 weeks) began 1 week after the initial biopsy. RNA was isolated from snap-frozen IEN lesions for microarray analyses, followed by quantitative reverse transcription-PCR validation. Additional epithelial gene-specific quantitative reverse transcription-PCR analyses facilitated the assessment of target tissue treatment effects. Surface epithelial COX-2 and iNOS protein levels and microvascular densities were determined by image analysis quantified immunohistochemistry. Topical berry gel application uniformly suppressed genes associated with RNA processing, growth factor recycling, and inhibition of apoptosis. Although the majority of participants showed posttreatment decreases in epithelial iNOS and COX-2 proteins, only COX-2 reductions were statistically significant. These data show that berry gel application modulated oral IEN gene expression profiles, ultimately reducing epithelial COX-2 protein. In a patient subset, berry gel application also reduced vascular densities in the superficial connective tissues and induced genes associated with keratinocyte terminal differentiation.
Assuntos
Ciclo-Oxigenase 2/genética , Frutas , Neoplasias Bucais/tratamento farmacológico , Óxido Nítrico Sintase Tipo II/genética , Fitoterapia , Lesões Pré-Cancerosas/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Western Blotting , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Ciclo-Oxigenase 2/metabolismo , Feminino , Géis , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Invasividade Neoplásica , Óxido Nítrico Sintase Tipo II/metabolismo , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologiaRESUMO
PURPOSE: The National Surgical Adjuvant Breast and Bowel Project B-24 trial, published in June 1999, demonstrated that tamoxifen after breast-conserving surgery (BCS) and radiotherapy for ductal carcinoma in situ (DCIS) reduced the absolute occurrence of ipsilateral and contralateral breast cancer. We assessed the impact of B-24 on practice patterns at selected National Comprehensive Cancer Network (NCCN) centers. PATIENTS AND METHODS: Tamoxifen use after surgery was examined among 1,622 patients presenting for treatment of unilateral DCIS between July 1997 and December 2003 at eight NCCN centers. Associations of clinicopathologic and treatment factors with tamoxifen use were assessed in univariate and multivariable logistic regression analyses. RESULTS: Overall, 41% of patients (665 of 1,622) received tamoxifen. The proportion increased from 24% before July 1, 1999, to 46% on or after July 1, 1999. Factors significantly associated with receipt of tamoxifen included diagnosis on or after July 1, 1999 (odds ratio [OR], 3.85; P < .0001), BCS in patients younger than 70 years (OR, 3.21; P = .0073), no history of cerebrovascular or peripheral vascular disease (OR, 3.13; P = .0071), receipt of radiotherapy (OR, 1.82; P = .0009), and previous hysterectomy (OR, 1.34; P = .0459). Tamoxifen use varied significantly by center, from 34% to 74% after BCS and 17% to 53% after mastectomy (P < .0001). CONCLUSION: Tamoxifen use after surgery for DCIS at NCCN centers increased after presentation of the B-24 results. Rates varied substantially by institution, suggesting that physicians differ in how they weigh the modest reduction in breast cancer risk with tamoxifen against its potential adverse effects in this population.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma in Situ/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Padrões de Prática Médica , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamoxifeno/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Carcinoma in Situ/cirurgia , Carcinoma Ductal de Mama/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Estados UnidosRESUMO
We review the use of three topical medications for the therapy of ocular surface tumors: mitomycin C, 5-fluorouracil, and interferon alpha-2B. One hundred sixty patients with histologically or cytologically proven epithelial and melanocytic tumors were identified in the literature. Side effects occurred most often with mitomycin C, followed by 5-fluorouracil, and interferon alpha-2B. Patients most frequently experienced transient keratitis, redness, and irritation. Topical agents were used as both primary and adjuvant therapy. Rates of tumor regression for CIN and squamous cell carcinoma ranged from 80 to 96%, and 70% of pigmented tumors regressed after an average follow-up of 27 months.