Combination chemotherapy with vincristine (NSC-67574), procarbazine (NSC-77213), prednisone (NSC-10023) with or without nitrogen mustard (NSC-762) (MOPP vs OPP) in children with recurrent brain tumors

Seventy-three patients under 18 years of age with a recurrent central nervous system tumor were randomized to receive combination chemotherapy with MOPP or OPP. Patients were stratified according to the tumor type into four major disease-categories: (1) medulloblastoma, (2) astrocytoma and other glioma, (3) ependymoma, and (4) miscellaneous tumors to provide equal distribution of patients for each treatment within each disease category. Evaluation of response was based on computerized brain scan findings. Thirty-five patients received MOPP and 38 received OPP treatment. There were three complete and six partial remissions among patients receiving MOPP and one complete and five partial remissions among patients receiving OPP. In addition, six patients on MOPP had stable disease for seven to 21 months. Only two patients on OPP had stable disease(6 and 36 months). Most of responses in both treatment regimens occurred in patients with medullo-blastoma and astrocytoma. Median duration of remission was ninemonths for the MOPP and 11 months for the OPP. Two patients on MOPP regimen had fatal myelosuppression. Although the more toxic MOPP regimen produced more responses than OPP in children, differences in the duration of response or survival were not statistically significant (P=.79 and P = .84, respectively).     

Combination chemotherapy with MOPP in children with recurrent brain tumors

Twenty-three children with CNS tumors were treated with combination chemotherapy including nitrogen mustard, vincristine sulfate, procarbazine, and prednisone (MOPP). All but one had progressive or recurrent tumors following surgery and irradiation. In addition, nine of these patients had prior chemotherapy. Seventeen out of 23 patients (73.4%) responded to MOPP chemotherapy including seven patients who had prior chemotherapy with single or multiple agents such as VCR, nitrosoureas, intrathecal methotrexate, and VM-26. Three comatose patients who were being kept on Decadron® without benefit recovered from coma. At the time of this report 8 of the 17 responders are surviving without evidence of recurrence 7–30 months from the start of MOPP chemotherapy. In two of these children chemotherapy has been completely stopped.     

伊立替康/替莫唑胺/长春新碱联合治疗儿童复发/难治实体瘤58例分析

目的探讨伊立替康/替莫唑胺/长春新碱治疗儿童、青少年复发/难治性实体瘤的疗效和毒性。方法从2011年9月-2014年4月,58例复发或难治儿童、青少年恶性实体肿瘤患者入组。采用替莫唑胺100 mg/(m2·d),口服,第1~5 d;伊立替康50 mg/(m2·d),在替莫唑胺口服1 h后静脉滴注,第1-5 d;长春新碱1.5 mg/m2,第1 d。每3周重复。每两个疗程评估疗效。结果 58例患者中,男32例,女26例。中位年龄6(1~18)岁。神经母细胞瘤28例,横纹肌肉瘤12例,尤文氏肉瘤/原始神经外胚叶瘤3例,肝母细胞瘤3例,横纹肌样瘤3例,肾母细胞瘤2例,生殖细胞瘤、骨肉瘤、间叶源性恶性肿瘤、纤维肉瘤、恶性外周神经鞘瘤、髓母细胞瘤和鼻咽癌各1例。化疗后完全缓解(CR)5例,部分缓解(PR)13例,稳定(SD)17例,进展(PD)23例。全组患者客观有效率(CR+PR)为31.0%,疾病控制率(CR+PR+SD)为60.3%。其中神经母细胞瘤有效率为39.3%;横纹肌肉瘤25.0%。共16例(27.6%)患者化疗后能获得局部治疗机会。神经母细胞瘤1年无进展生存率和总生存率分别为(23.4±10.8)%和(39.0±11.0)%。主要毒性为骨髓抑制和腹泻,对症处理可恢复。结论伊立替康/替莫唑胺/长春新碱联合方案是儿童、青少年复发/难治实体瘤有效的挽救化疗方案,毒性可耐受。     

Treatment of Hodgkin's disease in children with alternating mechlorethamine,vincristine, procarbazine,and prednisone (MOPP) and adriamycin,bleomycin, vinblastine,and dacarbazine (ABVD) courses without radiotherapy

Since the introduction of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, children with Hodgkin's disease (HD) have been treated with chemotherapy alone. The occurrence of side effects related to irradiation (especially secondary solid tumors) is less likely to occur. Alkylating agents in the MOPP chemotherapy combinations are, however, known for their late effects, i.e., gonadal dysfunction and secondary malignancies. Combination with non-alkylating and non-cross-resistant drugs (as in the adriamycin, bleomycin, vinblastine, and dacarbazine [ABVD] combination) may give superior treatment results and possibly a decrease in the occurrence of side effects. From 1988 to 1993 all children presenting with HD were treated with alternating MOPP and ABVD courses (3 × MOPP, 3× ABVD). Twenty-one children (7 females, 14 males), ages 5–18 years (median 14 years) were included; their clinical stages were 1, 7 patients; II, 8 patients; III, 5 patients; IV, 1 patient. Their pathology revealed 2 lymphocytic predominance, 17 nodular sclerosis, 1 mixed cellularity. In 1 patient only cytology was done and thus histopathologic subclassification was not possible. Two children have relapsed; disease-free survival is 90%. Analysis of toxicity revealed no decrease in cardiac function by ultrasound examination and no pulmonary effects noted by carbon monoxide diffusion. In 1 of the 10 children tested, mild hypogonadism was noted. No secondary tumors occurred. From this small population of children with HD we conclude that treatment with MOPP/ABVD for 6 cycles without radiotherapy may be adequate. The occurrence of gonadal dysfunction may be less frequent than with 6 cycles of MOPP. However, more patients and further follow-up are needed. Med. Pediatr. Oncol. 29:23–27, 1997. © 1997 Wiley-Liss, Inc.     

Liposomal daunorubicin (DaunoXome) in children with recurrent or progressive brain tumors

Liposomal daunorubicin (DaunoXome = DNX) has been used in 14 children with recurrent or progressive growing brain tumor. DNX was given as a 1-h intravenous infusion with a dose of 60 mg/m2, once every 4 weeks, up to a cumulative dose of 600 mg/m2. At 3-month intervals the tumor process was evaluated on MRI or CT scan. Tumor response and toxicity of DNX were recorded according to the WHO guidelines. In 6 of the children a response has been established: 2 had complete responses, of which one relapsed again after 3 months; in 3 children a partial response was found. Two children showed stable disease. In 6 children the tumors grew progressively. In all responding children a remarkable subjective response was found. The toxicity of DNX at this dose was mild with a mild bone marrow depression and a slight but certain cardiotoxicity in 3 children. For the whole group the left ventricular function decreased with 13.8%. In 1 child the DNX treatment was stopped because of a decrease of the shortening fraction to 20%. In 4 children some hair loss was observed at the end of the treatment. In 3 children mental depression occurred that was associated with the administration of DNX. DNX is a well-tolerated and effective drug in the treatment of slowly progressive or recurrent brain tumors in children.     

Combination chemotherapy with adriamycin (NSC-123127) and dimethyl triazeno imidazole carboxamide (DTIC) (NSC-45388) in children with metastatic solid tumors

Combination chemotherapy with adriamycin and DTIC was used in 102 evaluable patients under 15 years of age who had previously treated metastatic solid tumors. Responses, defined as 50% or more reduction in all tumor masses, occurred in 10 out of 27 patients with neuroblastoma, 3 out of 8 patients with Wilms tumor, 7 out of 15 patients with Ewing sarcoma, 2 out of 6 patients with osteosarcoma, 5 out of 13 patients with rhabdomyosarcoma, and 15 out of 33 patients with miscellaneous tumors which included a patient who had a complete regression of an extensive juvenile angiofibroma. Response rate to combination chemotherapy with adriamycin and DTIC in patients with Ewing sarcoma was significantly superior to the response rate obtained with adriamycin alone in another Southwest Oncology Group Study. Major toxicity included nausea, vomiting, myelosuppression, high incidence of pneumocystis carinii pneumonia (5 patients) and congestive heart failure (4 patients). There were 7 drug-associated deaths due to sepsis (1), pneumocystis carinii pneumonia (4), and congestive heart failure (2).     

A preliminary study of cyclophosphamide (NSC-26271), adriamycin (NSC-123127), imidazole carboxamide (NSC-45388), and actinomycin D (NSC-3053) with or without MER-BCG in patients with advanced sarcomas

Polychemotherapy for soft tissue sarcomas has been reported to produce response rates ranging from 24--60% (1, 2). Immunotherapy has reportedly prolonged survival after surgery for some tumors and enhanced the effectiveness of chemotherapy (3, 4). This report summarizes our preliminary experience with the combination of cyclophosphamide, adriamycin, imidazole carboxamide (DTIC), and actinomycin D (CAIA) with or without methanol extraction residue of BCG (MER) in patients with advanced sarcomas.