Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Child, Preschool ; Cyclophosphamide ; administration & dosage ; Female ; Humans ; Male ; Neuroblastoma ; drug therapy ; Topotecan ; administration & dosage ; Vincristine ; administration & dosage

BACKGROUND: Hepatocellular carcinoma remains a highly chemoresistant neoplasm and is a common malignancy with poor prognosis in Korea. We performed a phase II study to evaluate the efficacy and toxicities of topotecan and cisplatin combination chemotherapy for advanced hepatocellular carcinoma. METHODS: Between November 1999 and May 2001, ten patients with histologically proven hepatocellular carcinoma were enrolled in this study. The median age was 54 (range: 53~74) years and all were male. Six patients demonstrated stage IV, 1 stage IIIC, 2 stage IIIB and 1 stage IIIA. Six patients showed a ECOG performance status of 1. The treatment regimen consisted of topotecan 1.25 mg/m2 and cisplatin 20 mg/m2 for 5 days. The treatment was repeated every 4 weeks. Toxicities were evaluated according to WHO toxicity criteria. RESULTS: All ten patients were evaluable for response and toxicity. There was only one patient who achieved partial response. The overall response rate was 10% (95% C.I.) and the response duration was 46 weeks. The median survival of all patients was 21 (range: 17~54+) weeks. During a total of 24 cycles, neutropenia of WHO grade 3 and 4 occurred in 33%, thrombocytopenia in 33% and anemia in 21%. In non-hematologic toxicity, diarrhea and hepatoxicity of grade 3 occurred in 1 and 2 patients, respectively. But there was no treatment-related death. CONCLUSION: When used in this dose and schedule, topotecan and cisplatin combination chemotherapy does not seem to be effective for patients with advanced hepatocellular carcinoma.
Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carcinoma, Hepatocellular/*drug therapy ; Cisplatin/*administration & dosage ; Human ; Liver Neoplasms/*drug therapy ; Male ; Middle Aged ; Topotecan/*administration & dosage ; Treatment Outcome

Up to now, no consensus has been reached on the standard salvage regimen for patients with refractory or relapsed acute myeloid leukemia (AML). This study was purposed to evaluate the efficacy and safety of combination chemotherapy composing of cyclophosphamide (Cy), cytosine arabinoside (Ara-C) and topotecan (CAT regimen) for 37 refractory or relapsed AML patients. The dosing regimen was as follows: Cy 300 mg/m2 by intravenous infusion, every 12 hours on days 1-3, topotecan 1.25 mg/m2 by intravenous continuous infusion over 6 hours daily on days 2 to 6, Ara-C 500 mg/m2 by intravenous infusion over 2 hours daily for 5 days on days 2-6. The results showed that all patients completed one cycle of chemotherapy. 12 patients (32.4%) achieved complete remission (CR), 2 (5.4%) achieved partial remission (PR), and the 23 remaining patients achieved no remission (NR). The overall response rate (RR) was 37.8%. Among 18 relapsed cases, 6 cases had CR (33.3%), 2 cases achieved PR (11.1%), and 10 cases were with NR (55.6%). Among 19 refractory cases, 6 had CR (31.6%), and 13 (68.4%) were with NR. There was no statistically significant difference in RR between refractory and relapsed groups (31.6% and 44.4%, respectively) (p=0.42). Myelosuppression was universal. Mild non-hematologic toxicities were mainly gastrointestinal, as nausea, vomiting, diarrhea. The incidence of severe (grade III-IV) non-hematologic toxicity, such as oral mucositis and infection was 37.8% and 86.5% respectively. Only one patient died of severe infection during the observation (within 28 days from start of chemotherapy). The time of median follow-up was 4 (0-33) months, the median overall survival (OS) was 4 (1.8-6.2) months. The median OS for responders was longer than that for non-responders (9 vs 2 months respectively, p=0.00). In conclusion, the CAT regimen of lower dose is well tolerated and has certain anti-leukemia effect, and worthy to be further investigated.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; administration & dosage ; Cytarabine ; administration & dosage ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Recurrence ; Topotecan ; administration & dosage ; Young Adult

OBJECTIVETo evaluate chemotherapy-related toxicity and the short-term efficacy of topotecan and cyclophosphamide as maintenance chemotherapy for stage IV neuroblastoma in complete remission.

METHODSThe clinical data of 16 children with stage IV neuroblastoma received 3 cycles of maintenance chemotherapy with topotecan (0.75 mg·m(-2)·day(-1), infused on days 0-4) and cyclophosphamide 250 mg·m(-2)·day(-1), infused on days 0-4). The two-year event-free survival after complete remission was recorded and the chemotherapy-related toxicities were evaluated according to the Common Terminology Criteria for Adverse Events of the National Cancer Institute.

RESULTSThe most common chemotherapy-related toxicity was bone marrow suppression and suppressions of neutrophils, hemoglobin and platelets, which occurred in all the patients mostly of grade III and IV. All the patients experienced episodes of infections, which were controlled effectively with antibiotics. Impairment of gastrointestinal and liver functions in these cases was mostly mild (grade I and II) and recovered after corresponding treatments. None of the patients exhibited damages in the nervous system or the renal or cardiac functions. After complete remission, the two-year event-free survival rate of these patients was 68.75% (11/16).

CONCLUSIONTopotecan plus cyclophosphamide for maintenance chemotherapy can be effective and relative safe for stage IV neuroblastoma in complete remission, thus giving a chance to those patients who choose not to have stem cell transplantation.

Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; administration & dosage ; adverse effects ; Female ; Humans ; Infant ; Maintenance Chemotherapy ; Male ; Neoplasm Staging ; Neuroblastoma ; drug therapy ; pathology ; Topotecan ; administration & dosage ; adverse effects ; Treatment Outcome

OBJECTIVETo evaluate the therapeutic and adverse effects of topotecan combined with cisplatin in the treatment of advanced squamous cell lung cancer and head and neck cancer.

METHODSTotally 126 patients with advanced squamous cell lung cancer and head and neck cancer, which were confirmed by tissue pathology or cytopathology, were treated with intravenous infusion of topotecan at the dose of 0.75-1.2 mg/m2 (for 5 consecutive days) combined with intravenous infusion of cisplantin at 25-30 mg/m2 for 3 consecutive days. Each treatment course consisted of two 21-day cycles of the treatment.

RESULTSNo complete remission was achieved in these patients, and 61 patients had partial remission, 53 had clinically stabilized disease and 12 had progressive disease. The total response rate was 48.4% among the patients, with the median survival time of 10.1 months and one-year survival rate of 36.7%. The major adverse effects were bone marrow suppression and alopecia.

CONCLUSIONTopotecan combined with cisplatin may achieve a favorable response in patients with advanced squamous cell lung cancer and head and neck cancer, and causes tolerable adverse effect without accumulative toxicity.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; Cisplatin ; administration & dosage ; Female ; Head and Neck Neoplasms ; drug therapy ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Topotecan ; administration & dosage ; Treatment Outcome ; Young Adult

BACKGROUND: Patients with transformed chronic myelogenous leukemia(CML) and advanced myelodysplastic syndrome(MDS) have poor prognosis. The aim of this study is to evaluate the feasibility of second chronic phase induction in accelerated phase(CML-AP) or blastic crisis of CML(CML-BC) and remission induction in advanced MDS by combining topoisomerase I inhibitor (topotecan) with topoisomerase II inhibitor(mitoxantrone). METHODS: Twenty-four evaluable patients were entered on this study with a median age of 34 years. Eighteen patients with transformed CML(7 CML-AP, 11 CML-BC) and 6 patients with advanced MDS were treated. Topotecan was administered as 1.5 mg/m2/day by continuous infusion over 24 hours daily for 5 days every 4 to 8 weeks until remission. To enhance the tumoricidal effects, mitoxantrone(12 mg/m2/day, Days 1-3) was added. RESULTS: Eight patients(33+ACU-) achieved a complete remission(CR). Four of 7 patients with CML-AP(57+ACU-), 2 of 4 patients with CML-lymphoid blastic crisis (-LBC)(50+ACU-) and 2 of 6 patients with advanced MDS(33+ACU-) had CR lasting more than 45 days(45 to 400 days). There was no CR in the patients with CML-myeloid blastic crisis(-MBC). The dose level of 1.5 mg/m2/day(7.5 mg/m2/course) of topotecan was well tolerated in all patients. Mucositis occurred in 69+ACU- of patients (severe in 5+ACU-) and diarrhea in 67+ACU-(severe in 8+ACU-). In addition, there were no new or unexpected toxicities in the patients who were treated at this dose(7.5 mg/m2/course). In patients who recovered their neutrophil count, the absolute neutrophil count(ANC) remained below 500/microL for a period of 13 to 58 days(median 21 days) and the time to ANC recovery was associated with pretreatment severity of bone marrow fibrosis(mainly CML patients). Likewise, in the patients who recovered unsupported platelets, the platelets remained below 20,000/microL for a period of 0 to 37 days (median 19 days). CONCLUSION: The combination of topotecan-mitoxantrone has shown modest activity in CML-AP, CML-LBC and advanced MDS with acceptable toxicities.
Adult ; Aged ; Antineoplastic Agents, Combined/therapeutic use+ACo- ; Antineoplastic Agents, Combined/adverse effects ; Female ; Human ; Leukemia, Myeloid, Chronic/drug therapy+ACo- ; Male ; Middle Age ; Myelodysplastic Syndromes/drug therapy+ACo- ; Topotecan/administration +ACY- dosage+ACo-

OBJECTIVETo evaluate the efficacy and toxicity of topotecan-based combined chemotherapy for refractory or relapsed hematologic malignancies.

METHODSTwenty-one patients with refractory or relapsed acute leukemia (AL), non-Hodgkin's lymphoma (NHL) or high risk myelodysplastic syndrome (MDS) were treated by topotecan with cytarabine, amsacrine or cyclophosphamide. All patients received a single course as salvage therapy.

RESULTSThe overall response rate of one course was 61.9% with 9/21 (42.9%) CR and 4/21 (19%) PR. Severe myelosuppression was observed in all patients. Agranulocytic time was 12.6 days in AL and 7.5 days in NHL. Sixteen of 21 patients received G-CSF 300 micro g/d All patients received supportive treatment of transfusion. Fever and documented infection developed in 15 patients. Non-hematologic toxicity was mild.

CONCLUSIONTopotecan-based combined chemotherapy has significant antitumour activity and acceptable toxicity as salvage therapy for high risk hematologic malignancies.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Marrow ; drug effects ; Child ; Female ; Humans ; Leukemia ; drug therapy ; Lymphoma, Non-Hodgkin ; drug therapy ; Male ; Middle Aged ; Topotecan ; administration & dosage ; adverse effects

OBJECTIVETo analyze the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) for patients with locally advanced non-small-cell lung cancer (LA-NSCLC).

METHODSClinical data of 251 patients with stage III (76 IIIA and 175 IIIB) NSCLC who received CCRT as initial treatment between Jan 2001 and Dec 2010 in our hospital were reviewed. A median total radiotherapy dose of 60 Gy (range, 50-74 Gy) were delivered. 174 patients were treated with IMRT, 51 with 3D-CRT and 26 with 2D-radiotherapy. EP chemotherapy regimen was administered in 112 patients, PC regimen in 99 patients, topotecan regimen in 18 patients and other regimens in the remaining 22 patients. The efficacy and toxicity of CCRT were retrospectively analyzed.

RESULTS244 patients were assessable for response, including 6 (2.5%) patients with CR, 183 (75.0%) with PR, 42 (17.2%) with SD and 13 (5.3%) with PD. At a median follow-up period of 20 months, the 1-, 3-, 5- year OS were 69.2%, 31.2%, 23.2%, respectively, and the median OS was 21 months. The 1-, 3-, 5- year PFS were 40.9%, 22.1%, 17.7%, respectively, and the median PFS was 10 months. Patients with stage IIIA NSCLC achieved better 5-year OS than that with IIIB NSCLC (29.2% vs. 20.7%, χ2=2.254, P=0.133). Failure pattern was assessable in 244 patients, including 61 (25.0%) locoregional progression alone, 55 (22.5%) distant metastasis alone and 77 (31.6%) with both. The rates of grade≥3 radiation pneumonitis, esophagitis and hematologic toxicity were 4.4%, 11.2% and 26.4%, respectively.

CONCLUSIONSCCRT provide stage III NSCLC patients favorable outcome with acceptable toxicity. CCRT is standard therapeutic approach for patients with unresectable locally advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; pathology ; therapy ; Chemoradiotherapy ; Cisplatin ; administration & dosage ; Cyclophosphamide ; administration & dosage ; Esophagitis ; etiology ; Humans ; Lung Neoplasms ; pathology ; therapy ; Neoplasm Staging ; Radiation Pneumonitis ; etiology ; Radiotherapy, Conformal ; Retrospective Studies ; Topotecan ; administration & dosage

OBJECTIVETo explore the value of adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in individualized treatment of recurrent epithelial ovarian cancer (REOC), and to evaluate the correlation between the in vitro chemosensitivity assay and clinical drug sensitivity.

METHODSSixty-nine REOC specimens were tested by ATP-TCA assay retrospectively. The patients were divided into strong sensitive, moderate sensitively and resistant groups according to the ATP-TCA assay results. The clinical results were evaluated according to imaging and serum CA125 analysis. The correlation between in vitro ATP-TCA assay and clinical outcome was statistically analyzed by χ(2) test. The progression free survival (PFS) and overall survival (OS) of each group were analyzed using Kaplan-Meier method.

RESULTSThe results of ATP-TCA assay had significant correlation with clinical outcome. The clinical chemotherapy outcome became better with increased drug sensitivity in vitro (χ(2) = 9.066, P = 0.004). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate for ATP-TCA method to predict the clinical chemotherapy sensitivity of REOC were 87.5%, 45.9%, 58.3%, 80.9% and 65.2%, respectively. The mean PFS of strong sensitive group, moderately sensitive group and resistant group were 187.1 days, 195.0 days and 60.3 days, respectively. The mean OS were 476.7, 335.7 and 237.5 days, respectively, following the start of TCA-directed therapy. The PFS and OS of the two sensitivity groups in vitro were significantly longer than that of the in vitro-resistant group (P < 0.01).

CONCLUSIONThe results of ATP-TCA assay are well correlated with clinical treatment responses. The assay may be an important and useful method for individualized chemotherapy for recurrent ovarian cancer.

Adenosine Triphosphate ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CA-125 Antigen ; blood ; Carcinoma, Endometrioid ; blood ; drug therapy ; metabolism ; Cystadenocarcinoma, Serous ; blood ; drug therapy ; metabolism ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Disease-Free Survival ; Doxorubicin ; administration & dosage ; Drug Resistance, Neoplasm ; Drug Screening Assays, Antitumor ; methods ; Etoposide ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Luminescent Measurements ; Neoplasm Recurrence, Local ; Ovarian Neoplasms ; blood ; drug therapy ; metabolism ; Paclitaxel ; administration & dosage ; Predictive Value of Tests ; Retrospective Studies ; Sensitivity and Specificity ; Survival Rate ; Topotecan ; administration & dosage

OBJECTIVETo observe the protective effect of ginsenosides (GS) or low dose of glucocorticoid dexamethasone (Dex) alone or combined in managing the liver injury and renal function after transcatheter arterial chemoembolization (TACE).

METHODS120 patients with primary liver carcinoma were randomly divided into four groups (A, B, C, D) with 30 patients in each. Group A was treated with placebo; group B with Dex; group C with GS and group D with Dex plus GS. The changes in liver and renal function after TACE were observe according to the WHO criteria for side effects of anti-cancer drug.

RESULTSCompared with group A, Dex combined with GS was able to reduce the level of TB, ALT/AST, BUN and Child-grade, which significantly protected the liver and kidney (P < 0. 05). However, Dex or GS alone could also improve some parameters of liver and renal function after TACE (P < 0.05).

CONCLUSIONDex combined with GS is effective in managing the liver injury and renal function after transcatheter arterial

Adult ; Aged ; Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Blood Urea Nitrogen ; Chemoembolization, Therapeutic ; adverse effects ; methods ; Creatinine ; blood ; Dexamethasone ; pharmacology ; therapeutic use ; Drug Therapy, Combination ; Epirubicin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Ginsenosides ; pharmacology ; therapeutic use ; Glucocorticoids ; pharmacology ; therapeutic use ; Humans ; Iodized Oil ; administration & dosage ; Kidney ; drug effects ; pathology ; physiopathology ; Liver Diseases ; etiology ; pathology ; prevention & control ; Liver Neoplasms ; blood ; therapy ; Male ; Middle Aged ; Prospective Studies ; Topotecan ; administration & dosage