Efectos adversos inmunomediados por inhibidores de PD-1 / PD-1 inhibitors immune-mediated side effects

Los anticuerpos monoclonales que inhiben los puntos de control PD-1 y CTLA-4 se usan actualmente en el tratamiento del melanoma y cáncer metastásico de pulmón de células no pequeñas, entre otros. Se refiere el caso de una paciente con cáncer de pulmón en tratamiento con pembrolizumab. La paciente se presentó con edema facial y parálisis facial periférica. En el laboratorio se observó la hormona tirotrofina (TSH) elevada y se llegó al diagnóstico de hipotiroidismo por pembrolizumab. Inició tratamiento con levotiroxina con mejoría clínica. Se presenta este caso por el importante papel del dermatólogo en el manejo multidisciplinario del paciente oncológico. (AU)

Monoclonal antibodies that inhibit PD-1 and CTLA-4 control points are currently used in the treatment of melanoma and metastatic non-small cell lung cancer, among others. The case of a patient, with lung cancer being treated with Pembrolizumab. The patient was presented with facial edema and peripheral facial paralysis and in the laboratory the elevated hormone Tyrotrophin (TSH) was observed, the diagnosis of pembrolizumab hypothyroidism was reached. She started treatment with levothyroxine with clinical improvement. This case is presented by the important role of the dermatologist in the multidisciplinary management of the cancer patient. (AU)

Citorreducción óptima en cáncer de ovario avanzado tratado con paclitaxel a dosis densa y carboplatino seguido de cirugía de intervalo en el Instituto Nacional de Enfermedades Neoplásicas del Perú / Optimal cytoreduction in advanced ovarian cancer treated with dose-dense paclitaxel and carboplatin followed by interval surgery at the Peruvian National Institute of Neoplastic Diseases

RESUMEN Objetivos. Determinar la tasa de citorreducción óptima en pacientes con cáncer de ovario avanzado que recibieron quimioterapia neoadyuvante con carboplatino y paclitaxel dosis densa seguido de cirugía de citorreducción de intervalo (CCI). Materiales y métodos. Estudio de una serie de casos retrospectiva de mujeres peruanas tratadas con quimioterapia neoadyuvante con carboplatino (AUC 6 mg/ml/min) y paclitaxel (80 mg/m2 semanal) seguido de CCI, en el Instituto Nacional de Enfermedades Neoplásicas durante el período 2010-2014. Resultados . Los 41 pacientes que alcanzaron cirugía de intervalo, tuvieron una mediana de edad de 59 años (rango: 47-73 años). En 37 (90,2%) pacientes se reportó histología de adenocarcinoma seroso de alto grado. Treinta y cuatro (82,9%) lograron citorreducción óptima y cinco (14,7%) respuesta patológica completa. La sobrevida libre de progresión al año y 2 años fueron 74,7% y 51,8%, respectivamente. La sobrevida global al año y 2 años fue 85,2% y 71,4%, respectivamente. El riesgo de progresión y muerte fue mayor en pacientes sin citorreducción óptima y pacientes con niveles de dosaje del antígeno carcinoembrionario 125 postoperatorio > 30 U/ml. Conclusiones . La neoadyuvancia con carboplatino y paclitaxel dosis densa logró una frecuencia elevada de citorreducción óptima. Los niveles de antígeno carcinoembrionario 125 postoperatorios y citorreducción óptima resultaron factores independientes de sobrevida libre de progresión y sobrevida global.

ABSTRACT Objectives. To determine the rate of optimal cytoreduction in patients with advanced ovarian cancer who received neoadjuvant chemotherapy with dose-dense carboplatin and paclitaxel followed by interval debulking surgery (IDS). Materials and Methods. A retrospective study of a series of cases of Peruvian women treated with neoadjuvant chemotherapy with carboplatin (6 AUC mg/mL/min) and paclitaxel (80 mg/m2 weekly) followed by IDS, at the National Institute of Neoplastic Diseases during the 2010-2014 period. Results. The 41 patients who made it to the interval surgery had a median age of 59 years (range: 47-73 years). In 37 (90.2%) patients, high-grade serous adenocarcinoma histology was reported. Thirty-four (82.9%) achieved optimal cytoreduction and five (14.7%), a complete pathological response. Progression-free survival at one year and two years was 74.7% and 51.8%, respectively. Overall survival at one year and two years was 85.2% and 71.4%, respectively. The risk of progression and death was greater in patients without optimal cytoreduction and in patients with postsurgery levels of carcinoembryonic antigen 125 > 30 U/mL. Conclusions. Neoadjuvant therapy with dose-dense carboplatin and paclitaxel achieved an elevated frequency of optimal cytoreduction. The post-surgery levels of carcinoembryonic antigen 125 and optimal cytoreduction were independent factors of progression-free survival and overall survival.

Platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer / 부인종양

OBJECTIVE: The concept of platinum sensitivity and cross-resistance among platinum agents are widely known in the management of recurrent ovarian cancer. The aim of this study was to evaluate two hypotheses regarding the validity of the concept of platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer. METHODS: In this retrospective study, the clinical data of patients with recurrent cervical cancer, who had a history of receiving cisplatin based chemotherapy (including concurrent chemoradiotherapy [CCRT] with cisplatin) and who received second-line chemotherapy at the time of recurrence between April 2004 and July 2012 were reviewed. RESULTS: In total, 49 patients-34 squamous cell carcinomas (69.4%) and 15 non-squamous cell carcinomas (30.6%)-were enrolled. The median age was 53 years (range, 26 to 79 years). Univariate and multivariate analysis showed that a platinum free interval (PFI) of 12 months has a strong relationship with the response rate to second-line chemotherapy. Upon multivariate analysis of survival after second-line platinum-based chemotherapy, a PFI of 12 months significantly influenced both progression-free survival (hazard ratio [HR], 0.349; 95% confidence interval [CI], 0.140 to 0.871; p=0.024) and overall survival (HR, 0.322; 95% CI, 0.123 to 0.842; p=0.021). In patients with a PFI of less than 6 months, the difference of progression-free survival between patients with re-administration of cisplatin (3.0 months) and administration of cisplatin analogue (7.2 months) as second-line chemotherapy was statistically significant (p=0.049, log-rank test). CONCLUSION: The concept of platinum sensitivity could be applied to recurrent cervical cancer and there is a possibility of noncross-resistance of cisplatin analogue with cisplatin.

Palonosetron versus granisetron in combination with aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with gynecologic cancer / 부인종양

OBJECTIVE: There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT3 receptor with/without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC. METHODS: We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT3 receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT3 receptor and dexamethasone with/without aprepitant. RESULTS: When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT3 receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT3 receptor antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001). CONCLUSION: The addition of aprepitant therapy was more effective than the control therapy of a 5-HT3 receptor antagonist, and dexamethasone in gynecological cancer patients treated with the TC regimen.

Weekly chemotherapy as Induction chemotherapy in locally advanced head and neck cancer for patients ineligible for 3 weekly maximum tolerable dose chemotherapy.

OBJECTIVE: To study the safety and efficacy of weekly chemotherapy as part of induction chemotherapy, in locally advanced head and neck cancer for patients, who are unfit for upfront radical treatment. MATERIALS AND METHODS: It is a retrospective analysis of on‑use weekly chemotherapy as Induction chemotherapy in locally advanced head and neck cancer, who are technically unresectable are unfit for upfront radical treatment. Induction chemotherapy given was a 2 drug combination of paclitaxel (80 mg/m2) and carboplatin AUC 2. The decision to give weekly induction chemotherapy was given on the basis of presence of 2 more following features: Poor performance status (ECOG PS 2‑3), presence of uncontrolled co morbidities, BMI below 18.5 kg/m2 and age more than 60 years. The Statistical Package for the Social Sciences software (SPSS version 16.0) was used for analysis. The response rates, toxicity (accordance with CTCAE vs. 4.02), completion rate (Cp) of radical intent treatment post neoadjuvant chemotherapy (NACT), progression‑free survival (PFS) and overall survival (OS) are reported. RESULTS: Fifteen patients were considered for such therapy. Fourteen out of fifteen patients completed NACT. The median numbers of planned weekly cycles were 6 (3-8). Response (CR + PR) was seen in 10 patients. Overall grade 3-4 toxicity was seen in 6 patients. No toxicity related mortality was noted. The calculated completion rate (Cp) of radical intent treatment post NACT was 46.7%. The median PFS and OS were 10.36 months (95% CI 6.73-14.00 months) and 16.53 months (95% CI 4.22-28.84). CONCLUSION: Use of induction chemotherapy with weekly regimen is safe and effective selected cohort of patients with locally advanced disease who are unfit for upfront radical treatment.

Concurrent Low Dose Carboplatin with Radiotherapy Versus Radiotherapy alone in Management of Locally Advanced Head and Neck Cancer Patients.

A prospective study was performed to evaluate the efficacy and safety of concurrent chemotherapy with single agent low dose Carboplatin and radiotherapy on survival, functional and quality of life outcomes in locally advanced head and neck cancer patients. Material and Methods : Sixty inoperable, previously untreated locally advanced head and neck cancer patients were planned to be treated with radical radiotherapy 66 Gy with concurrent single agent chemotherapy with low dose Carboplatin 150 mg IV weekly up to 6.3 weeks (Group A) and conventional radical radiotherapy alone (Group B). Results : After completion of therapy in Group A complete response was observed in 19/30 (63%) patient and in control group B in 10/30 (33%).Grade II mucosal toxicities were observed in 40% of cases and 33 % of cases in study and control group respectively. Conclusion : Concomitant single agent chemo radiotherapy with low dose Carboplatin could be a better choice in advanced stage of Head and Neck carcinoma in terms of survival, acceptable toxicities together with enhanced response and quality of life.

Gemcitabine in brief versus prolonged low-dose infusion, both combined with carboplatin for advanced non-small cell lung cancer.

Purpose: Gemcitabine in low-dose prolonged infusion is a treatment with documented activity against a variety of tumors. The present study was conducted to evaluate the efficacy and safety of the combination of gemcitabine at a low-dose prolonged infusion in comparison with standard dose gemcitabine with carboplatin in chemonaive patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Sixty chemonaive patients with stage IIIB or IV NSCLC were included. Patients were randomly assigned 1:1 to receive 350mg/m 2 gemcitabine in a 6-h infusion on days 1 and 8 and carboplatin area under the serum concentration time curve (AUC) 5 on day 1 versus gemcitabine 1000mg/m 2 on days 1 and 8 and carboplatin AUC 5 on day 1 (3-week cycle both). A total of 118 chemotherapy cycles, with a median of 4 cycles per patient (range 2-6), and 134 chemotherapy cycles, with a median of 4.47 cycles per patient (range 3-6) were administered in standard and low infusional dose arm, respectively. Results: Among patients in the standard arm, 40% had overall response rate (ORR), 33.3% had stable disease and 26.6% had progressive disease, while in low-dose infusional arm, 36.6% had ORR, 36.3% had stable disease and 26.6% had progressive disease (P = 0.992). Median progression-free survival was 5.5 months and 5.4 months, median overall survival was 9.7 months and 10.7 months, and 1-year survival was 33.7% and 36.6% in standard arm and low-dose infusion arm, respectively. Grade 3/4 toxicity was rare. Conclusion: In NSCLC, gemcitabine low-dose prolonged infusion with carboplatin has low toxicity, especially thrombocytopenia, and has an activity comparable with gemcitabine given in higher dose in standard infusion.

Combination of gemcitabine and carboplatin in urothelial cancer patients unfit for cisplatin due to impaired renal or cardiac function

PURPOSE: Combination of gemcitabine and carboplatin is the accepted treatment for metastatic urothelial cancer patients unfit for cisplatin-based chemotherapy. MATERIALS AND METHODS: Gemcitabine 1000 mg/m² (days 1, 8) and carboplatin AUC-4.5 (day 1) were given every 21 days to 23 patients with creatinine clearance < 60 mL/min, cardiac ejection fraction < 45% or active ischemia. Patient characteristics included: median age 73 (56-86) years; primary site: bladder 17 (73%), upper tract 6 (27%) patients; Bajorin's prognostic groups: good 6 (26%), intermediate 11 (48%) and poor 6 (26%) patients. Data was retrospectively documented. Patients were followed until they expired. RESULTS: We obtained objective responses in 8 (34.7%) patients, (95% CI, 16.3-57.2%), including one patient with complete response. The median progression-free survival was 4 (0.2-16.5+) months and the overall survival 8.6 (0.2-45.3+) months. At time of analysis, 4 patients (17%) remained disease free; 3 of them underwent resection of residual disease. Toxicity included: infection in 9 (39%) patients; among them, one died from pneumonia; bleeding > grade 2 in 3 (13%) patients and fatigue grade 3 in 2 (9%) patients. Hematologic toxicity included grade 4 thrombocytopenia in 2 (9%) patients and grade 4 neutropenia in 3 (13%) patients. Five (22%) patients discontinued therapy due to toxicity. CONCLUSIONS: Combination of gemcitabine and carboplatin demonstrated clinical activity in patients with advanced urothelial cancer unfit for cisplatin. It was associated with considerable toxicity. Resection of residual disease is feasible in this population.

Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Young Children with Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

The feasibility and effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) were evaluated in children younger than 3 yr of age with atypical teratoid/rhabdoid tumors (ATRT). Tandem HDCT/autoSCT was administered following six cycles of induction chemotherapy. Radiotherapy (RT) was administered if the tumor relapsed or progressed, otherwise, it was administered after 3 yr of age. Tumors relapsed or progressed during induction chemotherapy in 5 of 9 patients enrolled; 3 of these 5 received tandem HDCT/autoSCT as a salvage treatment. One patient died from sepsis during induction chemotherapy. The remaining 3 patients proceeded to tandem HDCT/autoSCT; however, 2 of these patients showed tumor relapse/progression after tandem HDCT/autoSCT. All 7 relapses/progressions occurred at primary sites even in patients with leptomeningeal seeding. Toxicities during tandem HDCT/autoSCT were manageable. A total of 5 patients were alive with a median follow-up of 20 (range 16-70) months from diagnosis. Four of 5 patients who received RT after relapse/progression are alive. The probability of overall survival at 3 yr from diagnosis was 53.3% +/- 17.3%. Our tandem HDCT/autoSCT is feasible; however, early administration of RT prior to tandem HDCT/autoSCT should be considered to improve the outcome after tandem HDCT/autoSCT.

Clinical Results of High-Dose Chemotherapy Followed by Autologous Peripheral Blood Stem Cell Transplantation in Children with Advanced Stage Rhabdomyosarcoma

Regardless of improvement in cure of Rhabdomyosarcoma (RMS), the results in treatment of advanced stage of RMS in children are still dismal. Recently, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (HDC/APBSCT) has been tried to manage the advanced high-risk RMS patients. We investigated the effectiveness of HDC/APBSCT by reviewing the clinical records of high-risk pediatric RMS patients in single institute database. Over twenty years, 37 patients were diagnosed as RMS with high-risk at the time of first diagnosis. These patients were classified as two groups according to treatment method. The first group was HDC/APBSCT and the other was conventional multi-agent chemotherapy group. Differences of clinical results between the two groups were analyzed. The median age of patients was 5 yr, ranging from 6 months to 15 yr. The 5-yr event free survival rate (EFS) of all patients was 24.8% +/- 4.8%. HDC/APBSCT group and conventional multi-agent chemotherapy group were 41.3% +/- 17.8% and 16.7% +/- 7.6% for 5-yr EFS, respectively (P = 0.023). There was a significant difference in the result of HDC/APBSCT between complete remission or very good partial response group and poor response group (50% +/- 20.4% vs 37.5% +/- 28.6%, P = 0.018). HDC/APBSCT can be a promising treatment modality in high-risk RMS patients.

Chemotherapy beyond first-line in stage IV metastatic non-small cell lung cancer / Quimioterapia em câncer de pulmão não pequenas células metastático estádio IV: além da primeira linha

OBJECTIVE: Platinum-based doublet chemotherapy is considered the standard of care for advanced non-small cell lung cancer (NSCLC). However, prognosis after recurrent or progressive disease following first-line chemotherapy is usually poor. Maintenance chemotherapy, second line treatment and even third line chemotherapy are available for patients with advanced NSCLC. Unfortunately, few patients are candidates for chemotherapy beyond first line. The present study evaluated characteristics of patients with NSCLC and outcomes of the treatment of their metastatic disease, with emphasis on second and third-line chemotherapy. METHODS: This was a retrospective observational study of 2,673 patients with metastatic, stage IV, non-small cell lung cancer admitted for treatment in two São Paulo institutions. First-line chemotherapy was defined as the first chemotherapeutic approach administered to the patient. Second and third-line chemotherapy were defined as the systemic treatment administered after discontinuing first-line chemotherapy, either for intolerance or for progressive or recurrent disease. RESULTS: Most patients (57.9 percent) received first-line chemotherapy, and approximately 23.4 percent received second-line and 8 percent third-line regimens. Only 2.5 percent received fourth-line chemotherapy. Median overall survival (OS) was 8 months (95 percent CI: 8-9 months). At univariate analyses, gender (p < 0.05), histology, first-line chemotherapy, objective response to first-line chemotherapy and second-line chemotherapy (p < 0.01) were prognostic factors related to overall survival. At multivariate analysis, only performance status (p = 0.04), receiving any second-line chemotherapy (p < 0.01) and response to first-line chemotherapy (p < 0.01) were independent predictors of overall survival. CONCLUSION: Second-line chemotherapy is a therapeutic strategy that should be considered for a selected group of patients. Performance status and response to first-line chemotherapy could be determinant characteristics to select patients who might be treated beyond first-line chemotherapy.

OBJETIVO: A quimioterapia dupla com base em platina consiste no tratamento padrão para o câncer de pulmão não pequenas células (CPNPC) avançado. Contudo, o prognóstico dos pacientes com doença recorrente ou em progressão após a quimioterapia de primeira linha é ruim. Quimioterapia de manutenção, de segunda linha e até de terceira linha são tratamentos válidos para pacientes com CPNPC de estádio avançado. Infelizmente, poucos pacientes são candidatos para o tratamento quimioterápico além daquele de primeira linha. O presente estudo avalia as características de pacientes com CPNPC e os resultados do tratamento da doença metastática, com ênfase na quimioterapia de segunda e de terceira linha. MÉTODOS: Este é um estudo observacional e retrospectivo de 2.673 pacientes com CPNPC metastático, estádio IV, admitidos para tratamento em duas instituições de São Paulo, SP. A quimioterapia de primeira linha foi definida como a primeira abordagem quimioterápica administrada ao paciente. Quimioterapias de segunda e de terceira linha foram definidas como tratamento sistêmico administrado após a interrupção da quimioterapia de primeira linha, seja por intolerância ou por doença em progressão ou recorrente. RESULTADOS: A maioria dos pacientes (57,9 por cento) foi submetida à quimioterapia de primeira linha; aproximadamente 23,4 por cento receberam quimioterapia de segunda linha e 8 por cento de terceira. Apenas 2,5 por cento foram submetidos ao regime de quarta linha. A sobrevida global mediana (OS) foi de 8 meses (IC 95 por cento: 8-9 meses). Na análise univariada, sexo (p < 0,05), histologia, quimioterapia de primeira linha, resposta imparcial à quimioterapia de primeira linha e quimioterapia de segunda linha (p < 0,01) foram fatores prognósticos relacionados com a sobrevida global. Na análise multivariada, status de performance (p = 0,04), submissão do paciente a qualquer tipo de quimioterapia de segunda linha (p < 0,01) e resposta à quimioterapia de primeira linha (p < 0,01) foram os únicos fatores independentes preditivos de maior sobrevida. CONCLUSÃO: A quimioterapia de segunda linha é uma estratégia terapêutica a ser considerada em seletos grupos de pacientes. O status de performance e a resposta à quimioterapia de primeira linha poderiam ser alguns dos fatores determinantes durante o processo de seleção dos pacientes que deverão ser submetidos a regimes quimioterápicos além da primeira linha.

Severe aseptic orbital cellulitis with subtenon carboplatin for intraocular retinoblastoma.

Retinoblastoma is a rare intraocular tumor of childhood. Chemoreduction followed by laser or cryotherapy is the treatment of choice. Subtenon carboplatin injection is also an accepted treatment modality for vitreous seeds, along with systemic chemotherapy. Transient periocular edema, optic neuropathy and fibrosis of orbital tissues are the known side effects of subteneon carboplatin injection. We report a case of severe aseptic orbital cellulitis with necrosis and prolapse of the conjunctiva 48 h after the injection, which resolved well on only conservative management.

In vivo growth of retinoblastoma in a newborn infant.

Retinoblastoma is a rare malignancy of the retina seen exclusively in children. It is known to cause rapid growth inside the eye and hence treatment should be started as soon as it is diagnosed. We report a case in a five-day-old infant in whom treatment (chemotherapy) was delayed by a month due to high bilirubin levels secondary to physiological jaundice, which gave us the unique opportunity to measure the growth of the tumor over a month. This case emphasizes that immediate treatment is warranted once this rare disease is diagnosed.

Neuroblastoma in an adult: Case report / Neuroblastoma en un adulto: Informe de un caso

El neuroblastoma es el tumor maligno sólido extracraneal más común en niños. Sólo el 10 por ciento de los casos se diagnostican después de la primera década de vida. Presentamos una paciente afroamericana de 23 años, con una masa paravertebral en T3-T5, múltiples lesiones en los cuerpos vertebrales y una lesión expansiva en la región parietal derecha. El estudio inmmunohistoquímico (negativo para CD99, CD20, CD3 y desmina y positivo para cromogranina, sinaptofisina y NB84), confirmó el diagnóstico de neuroblastoma. La paciente fue sometida a 12 ciclos de quimioterapia recibiendo VAC (vincristina / doxorubicina/ cyclofosfamida) intercalada con ICE (ifosfamida/ mesna/ etoposido). La doxorubicina fue reemplazada por actinomicina en el séptimo ciclo. La paciente toleró bien la quimioterapia y está clínicamente estable.

Neuroblastoma is the most common extracranial solid malignancy in children but rarely described in adults, being 10 percent of all cases diagnosed after the first decade of life. We report a 23 year-old black woman with a mass at paravertebral region of T3-T5, multiple lesions in vertebral bodies and expanding skull-brain lesion at the right parietal region. Immunohistochemical analysis (negative for CD99, CD20, CD3 and desmin; and positive chromogranin, synaptophysin and NB84) confi rmed the diagnosis of neuroblastoma. The patient was submitted to 12 cycles of chemotherapy receiving VAC (vincristine/doxorubicin/cyclophosphamide) interspersed with ICE (ifosfamide/mesna/etoposide) and doxorubicin was replaced by actinomycin in the 7th cycle. She had good tolerance to this therapy, and has been clinically stable.

Evaluation of paclitaxel and carboplatin versus combination chemotherapy with fluorouracil doxorubicin and cyclophosphamide as a neoadjuvant therapy in patients with inoperable breast cancer

To compare the results of patients with locally advanced breast cancer receiving two different regimens Fluorouracil, Doxorubicin and Cyclophosphamide [FAC] and Paclitaxel and Carboplatin. Comparative study. The Oncology Department, Institute of Nuclear Medicine and Oncology [INMOL], Lahore, from March 2007 to September 2008. Patients with inoperable locally advanced breast cancer of stage were included. Sixteen patients were given FAC regimen and 9 patients were given Paclitaxel and Carboplatin, each combination was cycled after 21 days for four times. Before enrollment, detailed medical histories, physical examinations and performance status assessments were done as well as postchemotherapy evaluation with regular follow-up visits was done. Complete Response [CR, xLlOO%] is defined as the disappearance of all known disease parameter i.e. disappearance in detectable tumour size, node free disease and surgery is possible. Paratial Response [PR, "L > 50%] was defined by 50% or greater decrease in the sum of the areas of bidimensionally measured lesions i.e. change of N2 to N1 or no status and some surgical procedure is possible to downstage the disease. Minor Response [MR] was defined as a decrease in the tumour insuffieceint to quality for partial responce. Static disease or no evaluable reflected no significant change in disease and no evidence of new disease. Progression of disease [> 25%] was defined as a 25% or greater increase in the area of any lesion > 2 cm or in the sum of the products of the individual lesions or the apprearance of new malignant lesions, surgery not possible. Twenty five patients completed neoadjuvant chemotherapy. Sixteen [66%] patients received FAC and 9 [37%] patients received PC chemotherapy. Overall CR [breast and axilla] was 54%, PR was 16% and minor response [MR] was 8%. FAC treatment induced more emesis, mucositis, alopecia and cardiotoxicity. No death occurred. The Paclitaxel and Carboplatin regimen was better tolerated; both regimens were effective in improving disease and overall survival

role of periocular carboplatin in treatment of advanced intraocular retinoblastoma

To evaluate the results of combined chemotherapy and periocular carboplatin injection to control advanced intraocular retinoblastoma [Rb]. In this prospective interventional case-series, we included 8 eyes of 8 patients with advanced intraocular Rb [group C or D in International Intraocular Retinoblastoma Classification, IIRC]. In these patients, periocular carboplatin was injected as a primary adjuvant therapy combined with chemotherapy [VEC regimen] or as a secondary treatment in patients who had recurrent disease or did not respond to primary chemotherapy and local modalities. All patients were examined under anesthesia [EUA] and fundus photography was done by Ret-cam before treatment. Fifteen miligrams of carboplatin was injected into subconjunctival or subtenon space in 3-4 weeks interval. Eight eyes of eight patients were enrolled. Five patients were male and three patients were female. Mean age of patients at the time of treatment was 34 months and the mean duration between initial presentation of Rb and beginning of treatment was 7.5 months. Mean injection of periocular carboplatin in each eye was 3.1 times. Past medical history in our patients before starting of this treatment included: External Beam Radiotherapy [EBRT] in 3 eyes, cryotherapy in 4 eyes, transpupillary thermotherapy [TTT] in 4 eyes and brachytherapy in 2 eyes. Four eyes were in group C and four eyes were in group D. In 3 patients carboplatin was injected as primary treatment and in five patients it was injected for tumor recurrence following initial treatment failure or relapse. Three patients had vitreous, one had sub-retinal and remaining four had both vitreous and sub-retinal seeding. The degree of seeding was low in two patients, moderate in two patients and severe in four patients. At the end of study, tumor was regressed in six eyes [75%], relapsed in one [12.5%] and recurred in another [12.5%]. In both eyes with relapsed and recurrent tumors, enucleation was done. Combined chemotherapy and periocular carboplatin injection as well as focal treatment may be an effective method to control advanced intraocular Rb

Determination of carboplatin dose by area under the curve in combination chemotherapy for senile non-small cell lung cancer / 华中科技大学学报（医学）（英德文版）

To preliminarily determine the appropriate dosage of carboplatin (CBP) at AUC of 5 mg.Ml(-1).min(-1) in the combination chemotherapy for Chinese senile patients with non-small cell lung cancer (NSCLC). Thirty-five Chinese senile patients with NSCLC in advanced stage (III/IV) were given 96 cycles of combination chemotherapy. Chemotherapy schedules included Taxol+CBP, Gemzar+CBP and NVB+CBP. The dose of CBP was at 5 mg.mL(-1).min(-1) of area under the concentration-time curve (AUC). Side effects and quality of life were observed before and after the chemotherapy. Myelosuppression was severe and commonly observed. Grade 3/4 of granulocytopenia was found in 47.9% (46/96) of the patients and grade 3/4 of thrombocytopenia was noted in 28.1% (27/96) of the subjects. However, other side effects were slight. The mean score of quality of life (QOL), according to the criteria of QOL for Chinese cancer patients had reduced 6.8. At 5 mg.mL(-1).min(-1) by AUC, the hematological toxicity of CBP was severe and it had some negative effects on the QOL. The administration of CBP at 5 mg.mL(-1).min(-1) by AUC may be too high for Chinese senile patients with non-small cell lung cancer.