Efficacy and tolerability of paclitaxel, ifosfamide, and cisplatin as a neoadjuvant chemotherapy in locally advanced cervical carcinoma / 부인종양

OBJECTIVE: To evaluate the efficacy and tolerability of a neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy in patients with locally advanced cervical carcinoma. METHODS: Patients with histologically confirmed locally advanced cervical carcinoma, aged > or =18 years, were treated with intravenous ifosfamide 5,000 mg/m2 and mesna 5,000 mg/m2, on day 1; intravenous paclitaxel 175 mg/m2 and cisplatin 75 mg/m2, on day 2; every 3 weeks for three cycles. Following chemotherapy, operable patients underwent radical hysterectomy and pelvic lymphadenectomy, and, if necessary, adjuvant radiotherapy. RESULTS: One hundred fifty-two patients with median age 53 years (range, 24 to 79 years), FIGO stage IIB in 126 (89%), were treated with chemotherapy for median 3 cycles (range, 1 to 3). Treatment was delayed or withdrawn in 23 patients (15%). One hundred thirty-nine patients (91%) underwent surgery. Postchemotherapy pathological complete response rate was 18% (25 patients). Postoperative radiotherapy was administered in 100 patients (72%). The 5-year overall survival and progression-free survival were 87.3% (95% confidence interval [CI], 84.5 to 90.3) and 76.4% (95% CI, 73.5 to 79.5), respectively. CONCLUSION: Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy was feasible and effective in the treatment of locally advanced cervical carcinoma patients with older age and more advanced disease stage than reported in previous studies. Hematological and renal toxicity could be carefully prevented.

ATP-Based Chemotherapy Response Assay in Primary or Recurrent Ovarian and Peritoneal Cancer

PURPOSE: To investigate chemosensitivity with an adenosine triphosphate-based chemotherapy response assay in patients with epithelial ovarian or peritoneal cancer according to tumor histology, grade, and disease status. MATERIALS AND METHODS: One hundred specimens were collected during primary or secondary debulking from 67 patients with primary ovarian cancer, 24 patients with recurrent ovarian cancer, 5 patients with primary peritoneal cancer, and 4 patients with recurrent peritoneal cancer; samples were collected between August 2006 and June 2009. Tumor cells were isolated and cultured for 48 hours in media containing chemotherapy. The chemosensitivity index (CI) was calculated as 300 minus the sum of the cell death rate at 0.2x, 1x, and 5x drug concentrations, and the CI values were compared. RESULTS: CI values were obtained from 93 of 100 patients. The most active agents against primary disease were ifosfamide and paclitaxel. For primary serous adenocarcinoma, paclitaxel and irinotecan were the most active, followed by ifosfamide. For clear cell carcinoma, ifosfamide was the most active, followed by paclitaxel and irinotecan. Although not statistically significant, the CIs of cisplatin, carboplatin, paclitaxel, and docetaxel decreased as tumor grade increased. In 14 cases of recurrent disease, paclitaxel was the most active, followed by ifosfamide and cisplatin. CONCLUSION: Ifosfamide and paclitaxel were the most active drugs for primary and recurrent disease. Therefore, we recommend further clinical studies to confirm the efficacy of paclitaxel, ifosfamide, and cisplatin combination chemotherapy for recurrent and primary ovarian cancer.

High-dose tamoxifen plus ifosfamide and anthracycline in a patient with angiosarcoma of the breast / Tamoxifen en dosis alta con ifosfamida y antraciclina en un paciente con angiosarcoma de mama

Although breast cancer is, unfortunately, not uncommon in women, a mere 0.04% of malignant breast tumours are primary angiosarcomas. Chemotherapy is advocated for treatment of breast angiosarcomas; however, no guidelines exist regarding optimal chemotherapeutics or protocols. Presently, the prognosis for breast angiosarcomas is poor. This case report describes a 24-year old woman diagnosed with primary breast angiosarcoma. She initially refused to receive treatment, but later returned to the hospital four years later with a haemopneumothorax. She was treated with rescue chemotherapy using a combination of high-dose tamoxifen plus ifosfamide and epirubicin (an anthracycline). She achieved a partial response, but died 16 months after therapy was initiated. More research is needed to devise novel chemotherapeutics and protocols to improve outcomes in women diagnosed with primary angiosarcomas ofthe breast.

Aunque el cáncer de mama, desafortunadamente, no es poco común en las mujeres, apenas 0.04% de los tumores malignos de mama son angiosarcomas primarios. La quimioterapia es el tratamiento de preferencia en los casos de angiosarcomas de mama. Sin embargo, no existen guías en relación con los protocolos o la quimioterapia óptima. En la actualidad, el pronóstico para los angiosarcomas de mama es pobre. Este informe del caso describe a una mujer de 24 años diagnosticada con angiosarcoma primario de mama. Inicialmente la paciente se negó a recibir tratamiento, pero volvió al hospital cuatro años más tarde con un hemoneumotórax. Fue tratada entonces con quimioterapia de rescate usando una combinación de alta dosis de tamoxifen con ifosfamida y epirrubicina (antraciclina). Llegó a responder parcialmente al tratamiento, pero falleció 16 meses después del inicio de la terapia. Se necesitan más investigaciones para elaborar nuevos quimioterápeuticos y protocolos que mejoren los resultados en los casos de mujeres diagnosticadas con angiosarcomas primarios de mama.

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.

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.

Phase II Study of Combination Chemotherapy with Etoposide and Ifosfamide in Patients with Heavily Pretreated Recurrent or Persistent Epithelial Ovarian Cancer

The aim of this trial was to investigate the efficacy and toxicity of combination chemotherapy with etoposide and ifosfamide (ETI) in the management of heavily pretreated recurrent or persistent epithelial ovarian cancer (EOC). Patients with recurrent or persistent EOC who had measurable disease and at least two prior chemotherapy participating in this phase II trial were to receive etoposide at a dose of 100 mg/m2/day intravenously (IV) on days 1 to 3 in combination with ifosfamide 1 g/m2/day IV on days 1 to 5, every 21 days. Thirty-seven patients were treated; about 78% had previously received more than two separate regimens. The response rate (RR) was 18.9% and median duration of response was 7 months (range, 1-15). Treatment free interval prior to ETI (TFI) has significant correlation with RR rate (P=0.034). Patients (n=6) with TFI > or =6 months had 50% of RR, while patients (n=31) with TFI or =6 months.

Fibrohistiocitoma maligno (fibroxantosarcoma) de cuero cabelludo: a propósito de un caso / Histiocytoma malignant fibrous (Fibroxantosarcoma) of scalp: a purpose of a case

Los tejidos blandos comprenden los músculos, tendones, la grasa, el tejido fibroso, el tejido sinovial, los vasos y los nervios. Alrededor del 60 por ciento de los sarcomas de tejidos blandos se originan en los miembros, siendo 3 veces más frecuentes en los miembros inferiores que en los superiores. En 30 por ciento de los casos se localiza en el tronco y en 40 por ciento son retroperitoneales. En el resto del 10 por ciento se trata de tumores de cabeza y cuello. La entidad denominada fibrohistiocitoma comprenden un gran número de tumores calcificados anteriormente como fibrosarcomas o como variedades polimorfas de otras sarcomas, y se caracteriza por una mezcla de células fusiformes (fibrosas) y células redondas (histiocitarias) dispuestas en un patrón estoriforme, junto con abundantes células gigantes y zonas de polimorfismo. La importancia de los estudios de inmunohistoquímica en los tumores de partes blandas radica en la necesidad que tiene el patólogo de precisar el diagnóstico histopatológico de lesiones benignas y malignas pseudosarcomatosas o sarcomatosas y poder diferenciarlas de neoplasias de otro origen. Se trata de paciente masculino de 65 años quien consulta por presentar desde agosto del 2006, caracterizado por lesiones ulcerosa en cuero cabelludo sangrantes quién se le tomo una primera biopsia que reporta. La nueva Biopsia tomada en enero en este centro reporta Carcinoma Epidermoide moderadamente a poco diferenciado en región fronto parietal de cuero cabelludo recibe 1 ciclo de quimioterapia, se toma una biopsia nueva reportando su inmunohistoquímica Fibrohistiocitoma Maligno (fibroxantosarcoma)/Tumor de Cuero Cabelludo, en vista de resultado se planifica nueva quimioterapia, se observo mejoría satisfactoria en la lesión en cuero cabelludo, por lo que decide oncología y el servicio de Medicina Interna dar de alta y seguir sus quimioterapias por consulta externa.

Recurrent episodes of hematuria: a rare presentation of leiomyosarcoma of prostate.

Leiomyosarcoma of the prostate is an extremely rare entity. Sarcomas account for about 1% of all malignant tumors and less than 5% of them arise from the genitourinary tract. Majority of patients present with urinary obstructive symptoms. The outcome is generally poor. Surgery with or without radiotherapy/chemotherapy forms the mainstay of treatment for patients with operable tumors. We report a patient presenting with recurrent episodes of hematuria.

Ifosfamide containing regimen for non-small cell lung cancer.

BACKGROUND: Combination chemotherapy has been demonstrated as one of the best active regimens in patients with non-small cell lung cancer (NSCLC). METHODS: A total of 206 patients with advanced unresectable NSCLC stage III B or stage IV were enrolled to receive combination chemotherapy with mitomycin, ifosfamide and cisplatin. About a third of them (n=63) did not continue therapy after the first course either because of toxicity, lack of affordability, or death. The remaining 143 patients (121 males) received two or more cycles of chemotherapy. RESULTS: Nearly half of all followed-up patients showed a partial or complete radiological response. Overall performance status (Karnofsky scale) worsened in 28 (19.6%) and improved in 44 (30.8%). While 50 patients (35%) gained weight, 65 (45.5%) lost weight during follow-up. Overall median survival was 20 weeks [95% confidence interval (CI), 16 to 24 weeks]. However, overall survival improved progressively with the number of chemotherapy cycles administered. Median survival in patients receiving at least three, four and five chemotherapy cycles was 23 (95% CI, 19-27); 27 (95% CI, 24-30) and 35 (95% CI, 28-42) weeks respectively. Survival at the end of three, six, nine and 12 months was 64.3%, 29.4%, 14.7% and 9.8%) respectively. Survival had no association with age of the patient, but was significantly correlated with baseline performance status (Pearson's correlation coefficient 0.29 p<0.01). The cost of each course of chemotherapy was a little over 100 US dollars. The side effects were minimal and acceptable, and the regimen was tolerated well by all the patients. CONCLUSION: Ifosfamide regimen containing mitomycin and cisplatin is a chemotherapeutic combination for treating patients with advanced NSCLC.

A Case of Renal Synovial Sarcoma: Complete Remission was Induced by Chemotherapy with Doxorubicin and Ifosfamide

We experienced a case of primary renal synovial sarcoma in a 32 year-old woman. On admission, she complained of intermittent abdominal pain. On radiologic examination, a 12 X 10 cm-sized soft tissue mass was detected on the left kidney. The tumor had histologic and immunophenotypic features that were consistent with spindle cell type monophasic synovial sarcoma. Four months after complete resection of the tumor, a unilateral hematogenous metastasis developed in the lung. She was treated with combined chemotherapy of doxorubicin and ifosfamide every four weeks, and complete remission was achieved. We herein describe the case with a brief review.

Phase 1 trial of ifosfamide and adriamycin metastatic breast cancer

A Phase I trial was conducted in patients with estrogen negative receptors [ER] or hormone refractory metastatic breast cancer to determine the maximum tolerated dose [MTD] of ifosfamide with a fixed dose of doxorubicin. A secondary objective was to determine the efficacy of the combination in metastatic breast cancer. Fifteen patients were entered in the study in cohorts of three patients at each dose level of ifosfamide. The dose of doxorubicin was fixed at 45 mg/m[2]. Five different dose levels of ifosfamide were tested ranging from dose level I of 1.5 gms/m[2]day 1-3 to level V at 2.5 gms/ m[2] day 1-3. Dose escalation of ifosfamide was stopped at 2.5 gms/ m[2]. The MTD of ifosfamide was 2.25 gms/ m[2] day 1-3 in combination with doxorubicin. All patients in the study were assessable for toxicity. Neutropenia and thrombocytopenia were the major dose limiting toxicities. Other toxicities included anemia, confusion and hematuria. Objective responses were documented in 11 of 15 patients [73.3 percent]. Median time to treatment failure [TTF] was 13 months. Median overall survival [OS] was 18 months. The combination of ifosfamide and doxorubicin was a practical well tolerated regimen. There was substantial evidence of clinical activity in this phase I trial. This combination should be further evaluated, as an attractive alternative to taxanes for patients in developing countries where cost effectiveness is important

Phase II study of ifosfamide, carboplatin, etoposide and GM-CSF in small cell lung cancer.

Twenty patients with small cell lung cancer (SCLC) were entered to the study. Fourteen cases were male and six cases were female. Twelve cases were extensive disease, eight cases were limited disease. Median age was 60 years (range = 40-72 years), median performance status was 70 per cent (range = 60-80%). All patients were treated with combination chemotherapy consisting of ifosfamide 5 g/m2 intravenous infusion over 4 hours with mesna uroprotection, carboplatin 300 mg/m2 intravenous infusion over 2 hours on day 1, and etoposide 120 mg/m2 intravenous infusion over 4 hours on day 1-3. Chemotherapy was re-cycled every 28 days. Assessment of hematologic toxicity (CBC) was performed two times per week. If there was grade 3 or 4 neutropenia on any cycle of chemotherapy, GM-CSF was administered for febrile neutropenia and on the next cycle it was administered prophylactically on day 4-14. RESULTS: Seventeen cases were evaluable for response and toxicity (three cases were inevaluable due to loss to follow-up after the first cycle of chemotherapy). Fourteen cases (five limited disease, nine extensive disease) achieved partial response (82.5%). Two cases had stable disease, one case died on day 7. One year survival was 23.5 per cent. Seventy and a half percent grade 3 and 4 neutropenia was seen during the first cycle. One patient had febrile neutropenia. After being prophylactically treated with GM-CSF, grade 3 and 4 neutropenia was reduced from 70.5 per cent to 56.2 per cent, 46.7 per cent, 63.6 per cent, 42.8 per cent and 0 per cent in cycle 2-6 respectively. Major toxicity of GM-CSF consisted of transient chest distress, chills, sweating and hypotension which subsided in 5-10 minutes. No fever or skin rash was observed. CONCLUSION: Combination of ifosfamide, carboplatin and etoposide (ICE) is an active regimen for small cell lung cancer. However, because of its severe myelosuppression, this regimen needs hematopoietic growth factor support, and GM-CSF was used in this study. The administration of GM-CSF rendered ICE chemotherapy to be given safely.

Simposio. Avances recientes con ifosfamida/mesna en el tratamiento de tumores sólidos malignos: etopósido, platino, ifosfamida y dexametasona como tratamiento de rescate en los linfomas no Hodgkin / Symposium on recent advances with ifosfamide/Mesna in the treatment of malignant solid tumors

Existen grandes avances en el manejo de los linfomas; desafortunadamente un porcentaje variable de casos recaerán a regímenes de primera línea. Se informan los resultados preliminares de 17 pacientes con diagnóstico de linfoma de Hodgkin refractarios a manejo de primera línea o refractarios. El esquema utilizado fue cada 3-4 semanas: combinación de etopósido 100 mg/m² por tres días, platino 100 mg/m² e ifosfamida 5g/m² fraccionados en tres días, mesna al 20 por ciento de la dosis diaria de ifosfamida por tres dosis; y dexametasona de 20 a 40 mg cada 24 horas por tres días. Trece de los 17 pacientes fueron evaluables para eficacia (dos aún en tratamiento; los otros dos abandonaron la terapia) y 16 fueron evaluables para toxicidad en 74 ciclos administrados. Se obtuvieron 11 respuestas totales (84 por ciento): seis respuestas (46 por ciento) Äcon supervivencia libre de enfermedad mínima de dos meses y máxima de 11 mesesÄ y cinco respuestas parciales (38 por ciento). La toxicidad más frecuente y grave fue neutropenia grado 4 (20 por ciento) con dos muertos por septicemia y plaquetopenia grado 4 (7 por ciento). El resto de los efectos tóxicos fueron leves y reversibles. No se observó toxicidad vasical. Concluimos que el esquema utilizado es efectivo, pero conlleva toxicidad grave en una cuarta parte de los ciclos. Consideramos que es conveniente incluir factores estimulantes de colonias en este tratamiento

Bleomycin, cisplatinum and ifosfamide infusion chemotherapy in advanced/recurrent cancer of cervix.

Twenty one patients age ranging from 26-70 years, with biopsy proven recurrent/advanced carcinoma of the cervix were treated with bleomycin, cisplatinum and ifosfamide infusion therapy. 88% patients reported subjective improvement. The objective response rate was 66.6% (Complete 38% and partial 28.5%). Side effects were mainly nausea, vomiting, and alopecia. Treatment related fever was common. Hematuria and reversible encephalopathy with ifosfamide were seen in three and two patients respectively. These results indicate that BIP infusion chemotherapy is an active and safe combination for treatment of advanced/recurrent cervical cancer.

Tratamiento del cancer de protasta avanzado hormonoresistente con difosfato de dietiletilbestrol (DES-P) e ifosfamida-mesna: estudio en fase II / Treatment of hormone resistant advanced prostatic neoplasm with diethylstilbestrol diphosphate (DES-P) and iphosfamide-mesna: phase II study

El empleo de dietiletilbestrol difosfato ha sido exitoso para el tratamiento del carcinoma de prostata hormonoresistente. En 44 pacientes con enfermedad medible con centelleograma oseo patológico, un índice medio de Karnofsky de 50 (rango 30-90), edad media 66 años (rango 46-79) y todos tratados previamente con estrógenos, fueron tratados con DES-P o con DES-P más IF/Mesna. Las características clínicas y de laboratorio previas al tratamiento, eran comparables. DES-P se administró a razón de 800 mg/m en infusión iv de 24 horas, disuelto en sol, destrosa 5% 1500 ml, durante 7 días consecutivos. El ciclo se repitió cada 28 días. En el plan con DES-P más IF/Mesna, DES-P se administró con igual metodología; IF/Mesna 5g/m en infusión iv de 24 horas, disuelto en 2000 ml de sol, dextrosa 5%, el día 8§. Los ciclos se repitieron cada 28 días. Se requirieron 2 ciclos para evaluar respuesta, de acuerdo al criterio del Proyecto Nacional de Cáncer de Prostata de los EEUU. La toxicidad hematológica fué leve; se observó hematuria microscópica en 3, y síntomas del SNC en 2 pacientes. El porcentaje de respuesta fué similar con ambos tratamientos, pero el tiempo medio de pregresión y la sobrevida, fueron significativamente superiores con DES-P ñ IF/Mesna