Comparison of two regimens of postoperative concurrent chemoradiotherapy in adult patients with grade III-IV cerebral gliomas / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the therapeutic efficacy of two regimens of postoperative radiotherapy with concurrent chemotherapy using temozolomide (TMZ) and teniposide (VM-26) plus semustine (Me-CCNU) in adult patients with grade III-IV cerebral gliomas.</p><p><b>METHODS</b>Ninety-six adult postoperative patients with grade III-IV cerebral gliomas were randomized into two groups (n=48) to receive 60 Gy radiotherapy with concurrent TMZ treatment (TMZ-RT group) and radiotherapy with VM-26 plus Me-CCNU treatments (VM-RT group). The adverse effects of marrow depression, gastrointestinal toxicity and acute radiation-induced brain injury were observed. The immediate effect and survival outcome of the patients were compared between the two groups.</p><p><b>RESULTS</b>No adverse effects beyond grade III were observed in the two groups. TMZ-RT group showed a significantly lower incidence of grade I-II adverse effects than VM-RT group (P<0.05). The median survival time and 1-, 2-, and 3-year survival rates of the patients in TMZ-RT group were 28 months, 72.9%, 54.2% and 31.3%, respectively, showing significant differences from those in VM-RT group (16 months, 62.5%, 33.3% and 16.7%, respectively, P<0.05).</p><p><b>CONCLUSION</b>Radiotherapy with concurrent TMZ chemotherapy is an effective regimen with mild toxicities for treatment of adult malignant cerebral glioma.</p>

Nimotuzumab in combination with chemotherapy for patients with malignant gliomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Nimotuzumab is a humanized monoclonal antibody targeted against epidermal growth factor receptor (EGFR). Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment. The aim of the present study was to evaluate the efficacy and side effects of nimotuzumab in combination with chemotherapy for patients with malignant gliomas.</p><p><b>METHODS</b>The patients received 200 mg of nimotuzumab infusion intravenously over 60 minutes once weekly for the first eight weeks and then once every two weeks until unacceptable toxicity or tumor progression occurred. Individualized chemotherapy was administered based on O(6)-methylguanine-DNA methyltransferase (MGMT) expression and previous chemotherapy responses in combined with nimotuzumab.</p><p><b>RESULTS</b>Fourteen patients received a total of 122 times of nimotuzumab ranging from 2 to 20 (median 7.5 times). Combined chemotherapy regimens included: continuous 21-day temozolomide (10 cases), standard 5-day temozolomide (2 cases), teniposide plus cisplatin (1 case), and teniposide plus nimustine (1 case). Partial response (PR) and stable disease (SD) were found in 3 patients (21.4%)and 6 patients (42.9%), respectively. Disease control rate (PR + SD) was 64.3%. The median progression-free survival (PFS) was 4 months (95%CI: 0.7 - 7.3) and PFS at 6 months was 30.6%. The most common toxicities include grade I-II neutropenia (2 cases), thrombocytopenia (2 cases), lymphopenia (1 case), nausea and vomitting (3 case) and asymptomatic transaminase increase (1 case). One patient developed grade IV neutropenia and thrombocytopenia. One patient developed nimotuzumab-related acneiform rash.</p><p><b>CONCLUSIONS</b>Nimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation.</p>

Effects of enucleation and chemotherapy in advanced intraocular and intraorbital retinoblastoma with or without radiotherapy / 소아과

PURPOSE: Radiotherapy is effective in local treatment for retinoblastoma. However, asymmetric facial hypoplasia after radiation is a serious late effect. This study was performed to investigate the effects of enucleation and chemotherapy with or without radiotherapy in advanced intraocular and intraorbital retinoblastoma. METHODS: Between 1985 October and 2006 December, the records of thirty five patients who were diagnosed as retinoblastoma at Yeungnam University Hospital were reviewed. Advanced intraocular and intraorbital retinoblastoma patients classified as Reese-Ellsworth group III, IV, and V and Grabowski- Abramson class II were selected for the study. RESULTS: Eighteen patients were enrolled in this study. All patients were enucleated and had received chemotherapy. Nine patients received radiotherapy and nine patients didn't receive radiotherapy. Tumor cells were found on resection margin of optic nerve in five of nine patients who received radiotherapy, but none of nine who didn't receive radiotherapy. Chemotherapy included vincristine, adriamycin, cyclophosphamide, VM-26, cisplatin before 2001, and vincristine, etoposide, and carboplatin after 2001. There were no recurrences or metastases in nine patients who didn't receive radiotherapy. But two of nine patients who received radiotherapy had metastases to brain. However, all survivors who received radiotherapy had significant facial asymmetry. CONCLUSION: In advanced intraocular and intraorbital retinoblastoma without tumor cell on resection margin of optic nerve, enucleation and chemotherapy without local radiotherapy appears to be safe for long-term survival. However, in those with tumor cells on resection margin of optic nerve, enucleation and chemotherapy with local radiotherapy seems to be necessary to improve survival.

Survivin antisense oligonucleotide induces lymphoma cells apoptosis and sensitizes the cells to chemotherapy / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of antisense oligodeoxynucleotide (ASODN) of survivin gene on apoptosis and chemotherapy sensitivity of lymphoma cell line Raji.</p><p><b>METHODS</b>Anti-survivin phosphorothioate ASODN was synthesized and transfected into Raji cells by lipofectin. MTT assay was used to detect cytotoxicity. Apoptosis was observed by fluorescence microscopy and flow cytometry. Survivin expression was determined by RT-PCR and Western-blotting.</p><p><b>RESULTS</b>(1) survivin ASODN inhibited the cells proliferation in a dose and time dependent manner. (2) A higher apoptosis rate (33.0%) could be induced in Raji cells by survivin ASODN as compared with that induced by the sense oligodeoxynucleotide (11.5%) (P < 0.05). (3) The expression of survivin mRNA and protein significantly decreased after treatment with survivin ASODN. (4) There was a significant increase of cell inhibition rate after exposure to the combination of survivin ASODN and Vm26 as compared to Vm26 or survivin ASODN alone (both P < 0.05).</p><p><b>CONCLUSION</b>Survivin ASODN is able to inhibit the proliferation of Raji cells, induce the apoptosis, and enhance the sensitivity of Raji cell to chemotherapy via specific down-regulation of survivin expression.</p>

Chemotherapy with higher or lower dose of teniposide combined with cisplatin and pingyangmycin for oral squamous cell carcinoma / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To compare the clinical efficacy and toxicity of teniposide (VM26) of higher dose with those of lower dose, both combined with cisplatin (CDDP) and pingyangmycin (PYM), in the treatment of patients with squamous cell carcinoma of oral and maxillofacial region (SCCOMR).</p><p><b>METHODS</b>Sixty-five patients with SCCOMR entered into this study prospectively. Thirty-three patients were treated with higher dose of VM26 (total dose was 320 mg) combined with CDDP and PYM (PTP1), the other thirty-two patients were treated with lower dose (total dose was 158 mg) of VM26 combined with CDDP and PYM (PTP2).</p><p><b>RESULTS</b>Thirty-three patients received a total of 38 cycles of PTP1. The overall response rate was 81.82% (27/33). Thirty-two patients received a total of 36 cycles of PTP2 and showed overall response rate by 81.25% (26/32). There was no significant difference between PTP1 and PTP2 groups in response rate (P > 0.05). But the blood toxicity was more severe in PTP1 group than in PTP2 group (P < 0.01). Bone marrow depression rate (1-4 stage) was 48.48% in PTP1 group versus 25.00% in the other group.</p><p><b>CONCLUSIONS</b>A high response rate of 81.25% and relatively slighter adverse events could be obtained for lower dose of VM26 combined with CDDP and PYM (PTP2). So, the chemotherapy schedule, PTP2, a novel teniposide based regimen in SCCOMR could be employed and spread in clinical practice.</p>

Primary central nervous system lymphoma: a report of 28 patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the clinical characteristics, reasonable mode of treatment and prognostic factors in patients with primary central nervous system lymphoma (PCNSL).</p><p><b>METHODS</b>Twenty-eight patients with PCNSL treated from 1989 to 2002 were retrospectively reviewed. The clinical characteristics, results of treatment and prognostic factors were analyzed by SPSS10.0 statistic software.</p><p><b>RESULTS</b>Of 28 patients, 18 men and 10 women with a median age of 52 years. The median survival time was 2 years (range 6 months-6 years). The 5-year survival rate was 21.4%. Nineteen patients had single-locus lesion and 9 multi-locus lesion, 78.6% of the patients were diagnosed as having B-cell origin, its main type being diffuse large cell lymphoma. According to international working formulation (WF), moderate-grade of histopathology was observed in 57.7% (15/28). Cox regression analysis revealed that single- or multi-locus lesion was only independent prognostic factor (P = 0.0417). Combined chemotherapy showed significant efficacy for those patients who had lesion of B-cell origin, high grade or multi-locus lesion, and the efficacy of irregular chemotherapy was better than that of regular chemotherapy.</p><p><b>CONCLUSION</b>Primary central nervous system lymphoma has a special prognostic factor. Chemotherapy plays a very important role in comprehensive treatment, irregular chemotherapy should be adopted as a regular treatment.</p>

Chemosensitivity testing of oral squamous cell carcinomas with teniposide / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the antitumor effectiveness of teniposide in oral squamous cell carcinomas (OSCC) and to find evidence for using teniposide for treatment of patients with OSCC.</p><p><b>METHODS</b>Seventy-five patients with OSCC from the School of Stomatology, Shanghai Second medical University during 1999 to 2001 were evaluated. Tumors were diagnosed pathologically, and drug sensitivity tested. The antitumor drugs tested were cisplatin (CDDP) and teniposide (VM-26). Fresh drug was diluted in complete medium at fold of five times of peak plasma concentration (PPC x 5) achieved by intravenous administration of clinical doses. The concentrations were VM-26 60 mg/L, CDDP 15 mg/L.</p><p><b>RESULTS</b>The MTT assay was performed in 75 of 81 patients (success rate 92.6%). The clinical stages of the 75 patients according to the UICC TNM classification of malignant tumors were 28 with stage IV, 34 with stage III, 11 with stage II and 2 with stage I. The pathological grades of the 75 patients according to three step classification were 18 with Grade I, 37 with Grade I approximately II and 20 with Grade III. At a drug concentration of PPC x 5, the inhibition rates of tumor cells for VM-26 and CDDP were 63.34% and 24.08%, respectively. The inhibition rates of tumor cells for VM-26 were significantly higher than those for CDDP (P < 0.01).</p><p><b>CONCLUSIONS</b>The inhibition rates of OSCC cells for VM-26 are significantly higher than for CDDP. VM-26 may be the first selected drug for treating patients with OSCC.</p>

Chemosensitivity testing of oral and maxillofacial cancer with biopsy specimens / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To determine the chemosensitivity in fresh biopsy specimen of human oral and maxillofacial cancer, and the differential chemosensitivity among those drugs used popularly in clinic.</p><p><b>METHODS</b>Human biopsy cancer cells were obtained from 150 oral and maxillofacial malignant tumors. The antitumor drugs tested using modified MTT assay were cisplatin (CDDP), 5-fluorouracil (5-Fu), Pinyangmycin (PYM), Paclitaxel (Taxol), Teniposide (Vm-26), Epi-adriamycin (E-ADM), Vindesin (VDS) and Methortrexatum (MTX).</p><p><b>RESULTS</b>The success rate of the MTT assay was 93.33% (140 of the 150 cases). At a drug concentration of Cmax x 5, the inhibition rates of oral tumor cells were 63.76% for Vm-26, 25.93% for CDDP, 25.86% for E-ADM, 23.52% for Taxol, 22.97% for PYM, 22.08% for 5-Fu, 18.42% for VDS and 18.93% for MTX. The inhibition rate of VM26 was significantly higher than any of other seven chemotherapeutic drugs (P < 0.05). Over forty percent patients with squamous cell carcinoma showed moderate chemosensitivity to VM-26, CDDP and E-ADM, and over forty percent cases with adenoid carcinoma showed moderate chemosensitivity to Vm-26, Taxol and E-ADM.</p><p><b>CONCLUSIONS</b>Most oral and maxillofacial cancers showed chemosensitivity to Vm-26, CDDP, E-ADM and Taxol. Vm-26, E-ADM and Taxol were more potent drugs than VDS, 5-Fu and MTX against oral and maxillofacial cancer cells. Chemosensitivity testing using modified MTT assay was useful in selecting antitumor drugs for patients with oral and maxillofacial cancers.</p>

Dento-maxillofacial abnormalities caused by radiotherapy and chemotherapy / 대한구강악안면방사선학회지

A case of dento-maxillofacial abnormality involving a 10-year-old male patient with a history of esthesioneuroblastoma is presented. This patient had been treated with 54 Gy (60)Co-gamma-radiation to the nasal cavity for 6 weeks and 6 cycles of combination chemotherapy of Cyclophosphamide, Cisplatin, Adriamycin, VM-26 (Teniposide), and DTIC (Dacarbazine) when he was 16 months of age. Five years after cessation of cancer therapy, he was disease free and transferred for extensive dental care to Kyung Hee University Dental Hospital. A clinical and radiologic follow-up over last 4 years showed root stunting, premature closure of the root apices, microdontia, developmental arrest, small crowns, and partial anodontia. Maxillofacial morphology evaluated by cephalometric analysis showed deficiency of maxillary development.

Mejoría en el pronóstico de la leucemia linfoblástica aguda en niños de un país en desarrollo: resultados del protocolo nacional chileno PINDA 87 / Improved outcome for acute lymphoblastic leukemia in children of a developing country: results of the chilean national trial PINDA 87

Un grupo oncológico pediátrico nacional, PINDA, reporta el primer protocolo prospectivo, no randomizado, para tratamiento de la leucemia linfoblástica (LLA), usando una versión modificada del protocolo de Berlín-Frankfurt-Munster (LLA BFM 86). Los objetivos de este estudio fueron clasificar inmunofenotipos, disminuir radioterapia de cráneo y comprobar si este protocolo podía mejorar la sobrevida de nuestros pacientes. Procedimiento: desde junio 1987 a junio 1992 se registraron 444 pacientes, no seleccionados; de ellos 425 fueron evaluables. La terapia fue estratificada según riesgo: riesgo bajo (RB), riesgo alto (RA) y riesgo muy alto (RMA). Los pacientes en RB y RA recibieron inducción con protocolo I, consolidación con protocolo M (RMA usó protocolo E), reinducción con protocolo II y mantención. Todos recibieron tratamiento de prefase con prednisona oral y metotrexato (MTX) intratecal. Radioterapia de cráneo solo en RA y RMA (12-18 Gy). Los siguientes cambios se introdujeron al protocolo LLA BFM 86: en protocolo M 1 g/m² en vez de 5 g/m²; en protocolo E, 1 g/m² de citarabina en vez de 2 g/m², la mitoxantrona e ifosfamida fueron sustituidas por teniposido y ciclofosfamida. Resultados: inmunofenotipo: LLA común 67,4 por ciento, LLA proB 14 por ciento, LLA T 10 por ciento, LLA preB 4,3 por ciento. La frecuencia de sobrevida libre de eventos (SLE) global a 5 años fue 60 por ciento ñ 2 por ciento error standard; según riesgo fue: RB 75 por ciento, RA 62 por ciento, RMA 28 por ciento con una mediana de seguimiento de 6,5 años (rango 4,5 - 9,5 años). La incidencia acumulada de recaída en sistema nervioso central SNC fue 5,4 por ciento. Conclusión: hemos tenido éxito en realizar un estudio a nivel nacional. Nuestra estrategia para adaptar el protocolo BFM fue efectiva para mejorar la SLE. La distribución por fenotipos es similar a otras series

Ifosfamide and Etoposide in Relapsed Refractory Childhood Acute Lymphoblastic Leukemia / 대한소아혈액종양학회지

BACKGROUND: The prognosis for children with relapsed acute lymphoblastic leukemia remains dismal. Ifosfamide has previously been shown to be active as a single agent and in combination with doxorubicin, etoposide, and teniposide in pediatric solid tumors, recurrent acute lymphoblastic leukemia and adult acute leukemia. We assessed the efficacy and the toxicity of the drug combination with ifosfamide and etoposide in patients with relapsed refractory acute lymphoblastic leukemia. METHODS: Between April 1995 and May 1996, twenty children aged 1 to 14 years with ALL in Catholic Medical Center, all heavily pretreated and in bone marrow relapse, were enrolled in this study. Drugs were given intravenously each day for 5 days at the following doses ; ifosfamide 1.8 g/m2/day, etoposide 100 mg/m2/day and mesna 1440 mg/ m2/day(as a uroprotectant) ; Cycles were repeated every 28 days for two cycles. RESULTS: 1) Twenty heavily pretreated patients were entered on study. At study entry, seventeen patients were in first relapse, two were in second relapse and one was in third relapse. 2) Six patients(30%) achieved complete remission, and eight patients(40%) achieved partial remission. Overall response rate was 70%. 3) Duration of remission ranged from 30 days to 230 days. 4) The toxicity of the regimen was tolerated. Moderate or severe toxicity evaluated on a per cycle basis included : neutropenia 52.5%, thrombocytopenia 45%, hemorrhagic cystitis 12.5% and mucositis 2.5%. 5) Two patients went on to bone marrow transplantation with histocompatibility matched sibling donors while in remission. CONCLUSION: The combination of ifosfamide and etoposide with mesna uroprotection has significant activity in relapsed refractory childhood lymphoblastic leukemia with tolerable toxicity. We recommended bone marrow transplantation after successful reinduction because of short remission duration of this regimen.

Leucemias agudas como neoplasias secundarias em criancas portadoras de linfomas avancados / Acute leukemias as secondary neoplasms in advanced childhood non-Hodgkin's lymphoma

Em 1985 foi iniciado, no Instituto da Crianca-HC-FMUSP, um programa terapeutico para linfomas nao Hodgkin, com resultados claramente superiores aos anteriormente obtidos no Servico. Sao descritos dois casos de pacientes que apresentaram neoplasias secundarias, e sua possivel implicacao com as drogas empregadas.

A Case of Neuroblastoma Presenting with Sudden Blindness / 영남의대학술지

Neuroblastoma is the most common extracranial solid tumor of childhood which presents various clinical symptoms depending on the primary and metastatic sites. However, it has been rarely reported that sudden onset of blindness was the chief complaint of neuroblastoma. A four years old boy was admitted to the Yeungnam University Hospital with the chief complaint of a sudden onset of blindness due to a distant metastasis of abdominal neuroblastoma to the sphenoid sinus. On admission, both side pupils were dilated without light reflex, fundoscopy showed pale optic disk, electroretinogram was subnormal and visual evoked potential showed no response. The liver was palpable in 3 ½ finger breadth from the right costal margin and adult fist sized mass was palpable in the right flank. Skull X-ray showed destructed sphenoid bone and clinoid process and brain CT scan showed tumor mass in the sphenoid sinus and left orbit. Ultrasonogram and CT scan of the abdomen showed large tumor masses around the right kidney and para-aortic and retropancreatic lymph node. IVP showed displaced right calyceal system with preserved contour. Left supraclavicular lymph node which appeared after admission was biopsied and it showed poorly differentiated neuroblasts. He was treated according to the multiagent chemotherapy schedule for stage IV neuroblastoma patient of children's cancer study group. Abdominal tumor masses and sphenoid sinus mass were markedly reduced after 2 courses of the combination chemotherapy of cyclophosphamide, vincristine, DTIC, adriamycin and VM-26. Eventhough the blindness was not improved, the patient has been in good clinical codition.