Intensive chemotherapy with or without stem cell rescue has become widely accepted for treatment of neuroblastoma because increased dose-intensity correlates with improved response rates. For neuroblastoma that is resistant to intensive chemotherapy, further use of high-dose therapy is unlikely to be beneficial. For disease that recurs after myeloablative consolidation, high-dose salvage therapy may not be feasible because of poor bone marrow reserve and may not be justified in view of its morbidity in the absence of a realistic chance for cure. One treatment option in these difficult clinical settings is chronic oral administration of low-dose etoposide. However, there has been a few clinical reports for the experience of oral etoposide for refractory neuroblastoma. We now present 2 cases of successful response of oral etoposide for refractory neuroblastoma.
Administration, Oral ; Bone Marrow ; Drug Therapy ; Etoposide* ; Neuroblastoma* ; Salvage Therapy ; Stem Cells

BACKGROUNDTreatment option for metastatic breast cancer (MBC) patients pre-treated with chemotherapy is limited. Oral etoposide has shown some promises in these patients. However, patients who received heavy prior chemotherapy may have poor tolerance to prolonged oral etoposide exposure. This study is a single-arm clinical trial that evaluates the efficacy and safety of short-term oral etoposide in Chinese patients with MBC who had received heavy prior therapy.

METHODSMBC patients receiving at least two chemotherapy regimens prior to the enrollment were treated with repeated cycles of oral etoposide (60 mg×m(-2)×d(-1) on days 1-10, followed by 11 days of rest). The primary end point was the progression free survival (PFS). The secondary end points were objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and toxicity profiles.

RESULTSThirty-two patients received 230 cycles of oral etoposide with a median of 6 cycles (range, 2-20 cycles) per patient. Eight patients (25%) had partial response (PR) and 14 patients achieved stable disease (SD). The ORR was 25%. Nine patients achieved SD for more than 24 weeks and CBR was 53%. The median PFS and OS were 5 (range, 1.5-17.0 months) and 16 months (range, 3.0-51.0 months), respectively. The patients who achieved clinical benefit had longer survival time than those who did not (25.0 versus 11.0 months, P<0.01). Among the 16 patients who received more than four regimens prior to this study, four patients achieved PR and four achieved SD for more than 24 weeks, with a CBR of 50%. The most common hematologic adverse events were anemia (43.8%) and neutropenia (38.5%). Nausea/vomiting (75.0%) and alopecia (62.5%) were the most frequent non-hematologic toxicities.

CONCLUSIONOral etoposide is effective and well tolerated in Chinese women with heavily pretreated MBC.

Administration, Oral ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; complications ; drug therapy ; Drug Administration Schedule ; Etoposide ; administration & dosage ; therapeutic use ; Female ; Humans ; Middle Aged ; Young Adult

OBJECTIVETo compare the efficacy and toxicity of the chemotherapeutic regimen containing pirarubicin and mitoxantrone on the treatment of relapsed or refractory acute myeloid leukemia (AML) in adults.

METHODSIn this open prospective multicentre study, we randomly assigned patients with relapsed or refractory AML to receive TAE regimen (pirarubicin+cytarabine+etoposide) versus MAE regimen (mitoxantrone + cytarabine + etoposide). The efficacy and toxicity were compared between the two groups.

RESULTS56 patients entered this clinical trial. The complete remission (CR) rate on TAE arm was 79.0% versus 55.6% on MAE arm with the overall response (OR) rates of 86.8% versus 88.9%, respectively. The CR was higher on TAE arm (P=0.035) but with no significant difference between the two groups regarding the overall response (OR) rate. The regimens were well tolerated in both groups. Hematologic and non-hematologic toxicity were similar except relatively lower the mean dosage of G-CSF, red blood cells and platelets transfusion on TAE arm. No significant differences were seen between the two groups regarding the overall survival and relapse free survival rates.

CONCLUSIONTAE regimen might be an effective salvage therapy in patients with relapsed or refractory AML.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Dactinomycin ; administration & dosage ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Etoposide ; administration & dosage ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Methotrexate ; administration & dosage ; Prospective Studies ; Recurrence ; Remission Induction

OBJECTIVETo evaluate the effectiveness of AML-XH-99-M3 protocol for treatment of acute promyelocytic leukemia (APL) in children.

METHODSThirty-three children with APL received AML-XH-99-M3 protocol treatment. The event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) were evaluated by the Kaplan-Meier medthod with SPSS13.0 software.

RESULTSThirty patients (90.9%) achieved a complete remission (CR) after one course of treatment. The total CR rate was 100%. Six patients (18.2%) relapsed in an average of 29.17 months (16-38 months). Two patients (6.1%) died. The 7-year EFS and DFS in the 30 patients were 73.4+/-9.4%. The overall survival rate was 91.2+/-6.0%. The difference of EFS was observed in patients receiving intermittent all-trans-retinoic acid (ATRA) administration or not in the maintenance therapy (88.9+/-10.5% vs 62.5+/-13.6%) (P<0.05).

CONCLUSIONSThe AML-XH-99-M3 protocol for the treatment of APL produced a higher CR rate and higher EFS, DFS and OS rates in children. Intermittent administration of ATRA in the maintenance therapy can improve EFS rate.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cytarabine ; administration & dosage ; Daunorubicin ; administration & dosage ; Etoposide ; administration & dosage ; Female ; Humans ; Infant ; Leukemia, Promyelocytic, Acute ; drug therapy ; mortality ; Male ; Tretinoin ; administration & dosage

OBJECTIVETo investigate the efficacy of liposomal doxorubicin together with etoposide and high dose methylprednisolone (DEP) as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis (HLH).

METHODSTotal 41 patients with refractory HLH were enrolled in this study. The efficacy of treatment with DEP regimen after 2 and 4 weeks were evaluated according to the United States Midwest Cooperative HLH Group.

RESULTSOf 41 refractory HLH patients, 28 were males and 13 females. The median age was 31(18-62) years old. The overall response rate (ORR) was 78.1%(32/41), including 12 patients (29.3%) achieved complete remission (CR) and 20 (48.8%) achieved partial remission (PR). The underlying disease of HLH were identified in 33 patients, including 1 case of primary HLH (CR), 20 cases of lymphoma associated HLH and 12 cases of EBV associated HLH. There were still 8 cases with unknown underlying disease. The 9 patients who had no response to DEP died within 2 to 4 weeks after salvage therapy. Twenty of the 32 patients who achieved PR or CR survived to undergo subsequent chemotherapy, allogenic hematopoietic stem cell transplantation (allo-HSCT) or splenectomy.

CONCLUSIONThe single-arm study suggested that DEP regimen appeared to be an effective salvage protocol for adult patients with refractory HLH.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Cisplatin ; administration & dosage ; Etoposide ; administration & dosage ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphohistiocytosis, Hemophagocytic ; drug therapy ; Male ; Middle Aged ; Prednisone ; administration & dosage ; Remission Induction ; Salvage Therapy ; Young Adult

OBJECTIVETo evaluate the combination chemotherapy regimen with floxuridine, dactinomycin, etoposide, and vincristine (FAEV) as primary treatment for gestational trophoblastic neoplasia (GTN).

METHODSClinical data and outcome of the patients with GTN from 1 January 2004 to 31 December 2009 were retrospectively reviewed. Totally 38 eligible patients had received at least one cycle of FAEV chemotherapy as primary treatment. The primary end points were response rate and toxicity of FAEV regimen.

RESULTSTotally 38 patients and 205 cycles of FAEV chemotherapy were included. Twenty-eight of these patients (73.6%) achieved serologic complete remission (SCR). Regimens were changed in 10 patients because of 5 with no response and 5 with intolerable toxicity. The most serious adverse events were greater than or equal to grade 3 neutropenia (31.6%), febrile neutropenia (7.9%), and greater than or equal to grade 3 thrombocytopenia (5.3%). During the follow-up, none relapsed.

CONCLUSIONFAEV is an effective regimen with manageable toxicity for patients with GTN as primary treatment, especially for patients with non-metastatic low or high risk GTN.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Dactinomycin ; administration & dosage ; Etoposide ; administration & dosage ; Female ; Floxuridine ; administration & dosage ; Gestational Trophoblastic Disease ; drug therapy ; Humans ; Middle Aged ; Pregnancy ; Retrospective Studies ; Treatment Outcome ; Vincristine ; administration & dosage ; Young Adult

OBJECTIVETo study the concentration change of chemotherapeutic agents in plasma and tissue after intraarterial and intravenous injection.

METHODSTen mature female New Zealand rabbits were divided randomly into two groups. Fluorouracil, etopiside, and cisplatin were injected into the rabbits through the ear vein in one group and through the internal iliac artery in the other group. Blood samples and the uterus tissue specimens were collected at various time points after injection. Drug concentration in plasma and tissue was determined by high performance liquid chromatography (HPLC) method. The data were analyzed by the pharmacokinetic program 3P97.

RESULTSRegular concentration change of the three drugs in plasma and tissue was observed after the intravenous and intraarterial injection, which met the two - compartment model. The pharmacokinetic parameters of the three drugs after intravenous and intraarterial injection were different. The peak concentration in plasma after intraarterial injection was lower than that after intravenous injection and the peak concentration and area under curve (AUC) value in tissue after intraarterial injections were higher than those after intravenous injection.

CONCLUSIONIntraarterial chemotherapy has advantages to intravenous chemotherapy in fluorouracil, etopiside and cisplatin. These advantages depend on the drug pharmacological properties.

Animals ; Antineoplastic Agents ; administration & dosage ; blood ; pharmacokinetics ; Cisplatin ; administration & dosage ; blood ; pharmacokinetics ; Etoposide ; administration & dosage ; blood ; pharmacokinetics ; Female ; Fluorouracil ; administration & dosage ; blood ; pharmacokinetics ; Injections, Intra-Arterial ; Injections, Intravenous ; Rabbits

This study evaluated the effects of prolonged primary chemotherapy in retinoblastoma. The data for 27 eyes in 22 children who were treated for retinoblastoma with up to 13 cycles of primary chemotherapy was reviewed. The chemotherapy consisted of etoposide, vincristine, and either carboplatin or ifosfamide. In bilateral retinoblastoma, 1 eye was in each Ia, Ib, and Va, according to the Reese-Ellsworth classification, 2 in each IIa, IIIa, and IIIb, 4 in IIb, and 5 in IVa. Enucleation was performed in 1 in IIa and 1 in Va. In unilateral, 1 was in each IIa, IIIa, IVa, IVb, and Vb, and 4 in Va. Enucleation was performed in 8 with the exception of 1 in IIa. Complete regression was observed in 17 eyes (12 patients). There was no toxicity severe enough to delay treatment. Prolonged primary chemotherapy can be considered as an alternative treatment for retinoblastoma in III or less.
Antineoplastic Agents/administration& dosage ; Antineoplastic Agents, Alkylating/administration& dosage ; Antineoplastic Agents, Phytogenic/administration& dosage ; Antineoplastic Combined Chemotherapy Protocols/*administration& dosage ; Carboplatin/administration& dosage ; Child, Preschool ; Drug Administration Schedule ; Etoposide/administration& dosage ; Eye Enucleation ; Human ; Ifosfamide/administration& dosage ; Infant ; Retinal Neoplasms/*drug therapy/surgery/ultrasonography ; Retinoblastoma/*drug therapy/surgery/ultrasonography ; Retrospective Studies ; Vincristine/administration& dosage

The study was aimed to evaluate the effect of IEMAD (modified MIME) composed of isofosfamide, VM26 or VP16, methotrexate, cytarabine, dexamethasone or methylprednisolone, in treatment of refractory or relapsed non-Hodgkin's lymphoma. Twenty-five patients with refractory or relapsed non-Hodgkin's lymphoma (11 refractory NHL patients, 14 relapsed NHL patients) were treated with IEMAD regimen. The results showed that the complete remission rate was 24.0% (6/25) and the partial remission rate was 28.0%, having an overall response rate of 52%. The median survival duration was 13 months and the median duration of progression-free survival was 8 months. The most frequent complications were gastrointestinal complaint (nausea, vomiting etc.) and myelosuppression. No treatment related mortality was found. It is concluded that the IEMAD (modified MIME) regimen may be a safe and effective regimen that can be used in treatment of patients with refractory or relapsed non-Hodgkin's lymphoma who did not respond to other regimens.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Cytarabine ; administration & dosage ; Dexamethasone ; administration & dosage ; Drug Administration Schedule ; Etoposide ; administration & dosage ; Female ; Humans ; Ifosfamide ; administration & dosage ; Lymphoma, Non-Hodgkin ; drug therapy ; pathology ; Male ; Methotrexate ; administration & dosage ; Middle Aged ; Mitoguazone ; administration & dosage ; Recurrence

OBJECTIVETo observe the supplementary effect of moxibustion and Guben Yiliu III (GBYL), a Chinese herbal compound preparation, in combination with chemotherapy.

METHODSEighty-one patients of mid-late stage malignant tumor were randomly divided into 3 groups: 16 in Group A treated with chemotherapy and placebo; 35 in Group B treated with chemotherapy and GBYL and 30 in Group C treated with chemotherapy and GBYL plus moxibustion. The short-term effect of treatment, changes of blood picture, cell mediated immune function and blood coagulation in patients were observed.

RESULTSAfter chemotherapy, the lymphocyte count was significantly lowered in Group A and B (P < 0.01), but not in Group C (P > 0.05); lymphocyte subset T3 raised significantly in Group B; the average level of T-lymphocyte subsets was reduced in Group A while it increased in the other two groups; and a bi-directional regulation on plasma fibrinogen concentration was shown in Group C (P < 0.05).

CONCLUSIONMoxibustion prevented dropping of lymphocyte count caused by chemotherapy. Combination of GBYL and moxibustion could prevent the lowering of T-lymphocyte subsets caused by chemotherapy, and moxibustion could regulate bi-directionally the patients' abnormality in part of blood coagulation mechanism.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Blood Coagulation ; Carboplatin ; administration & dosage ; Cisplatin ; administration & dosage ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Drugs, Chinese Herbal ; therapeutic use ; Etoposide ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Humans ; Lung Neoplasms ; blood ; immunology ; therapy ; Lymphocyte Count ; Male ; Mitomycin ; administration & dosage ; Moxibustion ; Phytotherapy ; Stomach Neoplasms ; blood ; immunology ; therapy ; T-Lymphocyte Subsets