Evaluation of topotecan monotherapy for relapsed small-cell lung cancer after amrubicin monotherapy failure / Journal of Rural Medicine

Objective: The utility of topotecan monotherapy for relapsed small-cell lung cancer (SCLC) after failure of amrubicin monotherapy has not been evaluated. We aimed to investigate the efficacy and safety of topotecan monotherapy in patients with relapsed SCLC after amrubicin monotherapy.Patients and Methods: We retrospectively analyzed data from 16 patients with relapsed SCLC who were treated with topotecan monotherapy after amrubicin monotherapy at our hospital.Results: The response rate, progression-free survival, and overall survival were 0%, 32.5 days (95% confidence interval [CI] = 18–51), and 112 days (95% CI = 55–267), respectively. The most common adverse events (grade ≥3) were leukopenia (31.3%) and thrombocytopenia (31.3%), followed by anemia, anorexia, edema, and lung infections.Conclusion: The efficacy of topotecan monotherapy for relapsed SCLC after amrubicin monotherapy is inconclusive. Therefore, further studies are warranted.

Comparison of the efficacy and safety of cisplatin, etoposide, and irinotecan combined with chemotherapy and topotecan monotherapy as second-line treatment for patients with sensitive relapsed SCLC / 中国肿瘤临床

Objective: To investigate whether combination chemotherapy with cisplatin, etoposide, and irinotecan was better than topotecan alone as second-line chemotherapy in patients with sensitive relapsed small cell lung cancer (SCLC). Method: Between September, 2014 and September, 2017, the patients'data were collected in Jilin Province Cancer Hospital. All patients were diagnosed with sensitive relapsed SCLC. Thirty-six patients received combination chemotherapy containing cisplatin plus etoposide plus irinotecan, and 42 patients received topotecan alone. Combination chemotherapy consisted of five 2-week courses of intravenous cisplatin 25 mg/m2 on days 1 and 8, intravenous etoposide 60 mg/m2 on days 1-3, and intravenous irinotecan 90 mg/m2 on day 8. Topotecan therapy consisted of at least one course of intravenous topotecan 1.5 mg/m2 on days 1-5, every 3 weeks. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and safety was assessed in all patients who received at least one dose of drugs. Results: PFS was significantly longer in the combination chemotherapy group [median 5.3 months, 95% confidence interval (CI) 4.3-5.8] than in the topotecan group (3.2 months, 95% CI: 2.7-4.0;P=0.0030); OS was also significantly increased in the combination chemotherapy group (median 16.3 months, 95% CI: 13.8-19.1) than in the topotecan group (13.1 months, 95% CI: 10.2-15.4; P=0.0097). The most common grade 3/4 adverse events were neutropenia [31 (86.1%) patients in the combination chemotherapy group vs. 28 (66.7%) patients in the topotecan group], anemia [26 (72.2%) vs. 10 (23.8%)], leucopenia [29 (80.6%) vs . 21 (50.0%)], and thrombocytopenia [13 (36.1%) vs . 11 (26.2%)]. One treatment-related death (febrile neutropenia with pulmonary infection) occurred in the combination chemotherapy group, and none occurred in the topotecan group. Conclusions:Combination chemotherapy with cisplatin plus etoposide plus irinotecan could be considered a treatment option in second-line che-motherapy for selected patients with sensitive relapsed SCLC. However, the combination chemotherapy group had a higher incidence of adverse events than the topotecan group, and appropriate drug dosages should be explored.

Periocular topotecan for vitreous seeds in retinoblastoma

Purpose: Refractory or recurrent vitreous seeds account for a large proportion of failure of eye salvage in retinoblastoma. The purpose of this study is to evaluate the efficacy of periocular topotecan (POT) in the management of vitreous seeds in retinoblastoma. Methods: Retrospective, interventional study of patients with retinoblastoma with vitreous seeds who received POT concurrent with intravenous chemotherapy (IVC). Results: Thirty-eight eyes of 35 patients received POT. Five eyes (13%) belonged to International Classification of Retinoblastoma group C, 23 eyes (61%) belonged to group D, and 10 eyes (26%) belonged to group E. Primary treatment included IVC with a combination of carboplatin, etoposide, and vincristine for a mean of 6 cycles (median 6; range 6–9). Concurrent to IVC from the fourth cycle onward, all patients received POT. Focal vitreous seeds were present in 20 eyes (53%) which received a mean of 3 injections (median 3; range 1–7). Diffuse vitreous seeds were present in 18 eyes (47%) which received a mean of 4 injections (median 5; range 1–7). At a mean follow-up of 8.5 months (median 5 months; range 1–15 months), regression of focal and diffuse vitreous seeds was achieved in 16 eyes (80%) and 8 eyes (44%), respectively. In all, 24 eyes (63%) had complete remission of vitreous seeds with POT given concurrently with IVC. Eye salvage was possible in 19 eyes (95%) with focal vitreous seeds and 12 eyes (68%) with diffuse VS. Enucleation was necessary for persistent vitreous seeds and viable tumor in five eyes (13%), viable tumor alone in one eye (0.02%), and recurrent vitreous seeds in one eye (0.02%). None of the patients developed systemic metastasis. Conclusion: POT administered concurrent with IVC is safe and effective in the initial management of vitreous seeds.

The short-term outcome of intravitreal injection with topotecan for refractory vitreous seeding from retinoblastoma / 中华眼底病杂志

Objective To observe and evaluate the short-term therapeutic effect of intravitreal injection with topotecan for refractory vitreous seeding from retinoblastoma (RB).Methods Eleven patients (11 eyes) of RB with refractory vitreous seeding (received intravenous chemotherapy,intra-arterial chemotherapy,intravitreal melphalan,laser,cryotherapy and subsequently developed refractory viable vitreous seeds) were enrolled in this study.There were 6 males (6 eyes) and 5 females (5 eyes).The aged from 9 to 44 months,with the mean age of 26 months.According to International Intraocular Retinoblastoma Classification,11 eyes were initially classified as group E (3 eyes),D (6 eyes),B (1 eye) or A (1 eye).All patients were received intravitreal injection with topotecan.A total of 32 intravitreal topotecan injections were performed with a mean of 2.9 injections (median 3 injections;range 2-4 injections).The mean follow-up was 10 months.The safety and effectiveness of intravitreal injection with topotecan for refractory vitreous seeding from RB were observed.Results Complete regression of vitreous seeds was achieved in 11 of 11 eyes (100％),including complete disappearance in 9 eyes and fibrosis in 2 eyes.None of the patients needed enucleation and occured ocular or systemic complications in the follow-up period.Conclusion Intravitreal injection with topotecan for refractory vitreous seeds from RB is effective and safe.

Stability of topotecan reversed lipid-based nanoparticles in artificial intestinal fluids / 国际药学研究杂志

Objective To establish an analytical method to investigate the protective effect of reversed lipid-based nanoparti-cle(RLBN)for topotecan(TPT)in artificial intestinal fluid. Methods Reversed lipid-based nanoparticle of TPT(RLBN-TPT)was prepared by the two-step methods of lyophilization and dissolution. An analytical method was established to determine the concentra-tions of both forms of TPT by high performance liquid chromatography(HPLC). Release curve of RLBN-TPT in simulated intestinal flu-id(SIF)was investigated to study the stability of TPT in gastrointestinal(GI)fluid. Results Both lactone and carboxylate forms of TPT were well separated and determined precisely by the optimized HPLC method. The calibration curves were linear within the range of 0.25-5μg/ml for both forms of TPT. Compared with free TPT,RLBN-TPT significantly improved the stability of TPT in SIF as the per-centage of carboxylate form was remarkably lower than the free TPT(P<0.05). Conclusion RLBN can significantly protect the TPT from hydrolysis in GI,which may lay the foundation for the deuelopment of oral chemotherapeutic drug with higher bioavailability.

Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan in patients with brain metastases from lung cancer / 肿瘤

Objective: To prospectively evaluate the preliminary efficacy and safety of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan in patients with brain metastases from lung cancer. Methods: Between March 2009 and March 2012, 38 lung cancer patients with brain metastases were prospectively recruited in concurrent radiochemotherapy (CRCT) group to receive whole-brain irradiation (40 Gy/20 fractions) plus three-dimensional conformal boost (for patients with no more than 3 lesions and the diameter ≥ 2 cm, a three-dimensional conformal localized boost was given to increase the dosage to 56-60 Gy) combined with concurrent topotecan (1.75 mg/m2, once a week for 4-6 weeks). Another 38 patients with brain metastasis from lung cancer were selected to be recruited in simple radiotherapy (SRT) group to receive simple radiotherapy in the same period. The efficacy and the adverse reactions were evaluated. All the patients were followed-up, and the survival was analyzed. Results: In CRCT group and SRT group, the median progression-free survival (PFS) time of intracranial metastases were 6 and 3 months, respectively; one-year PFS rates were 42.8% and 11.6%, respectively; two-year PFS rates were 21.6% and 8.7%, respectively; the PFS of CRCT group was higher than that of SRT group (χ2 = 6.020, P = 0.014). In CRCT group and SRT group, the median survival (OS) time were 13 and 10 months, respectively; one-year OS rates were 50.8% and 40.4%, respectively; twoyear OS rates were 37.9% and 16.5%, respectively; the OS of CRCT group was not obviously higher than that of SRT group (χ2 = 1.811, P = 0.178). In CRCT group and SRT group, the one-year control rates of intracranial metastases were 75.9% and 41.6%, respectively; two-year control rates of intracranial metastases were 65.2% and 31.2%, respectively; there was a significant difference between the CRCT group and SRT group (χ2 = 3.892, P = 0.049). In CRCT group and SRT group, the one-year control rates of extracranial lesions were 47.8% and 32.5%, respectively; two-year control rates of extracranial lesions were 28.7% and 24.4%, respectively; there was no significant difference between the CRCT group and SRT group (χ2 = 0.610, P = 0.435). The major adverse reactions were myelosuppression and gastrointestinal reactions with no significant difference between the two groups (P > 0.05). Conclusion: Compared with simple radiotherapy, whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan can significantly improve the PFS rate and the control rate of intracranial lesion in patients with brain metastases from lung cancer, and no significant increase in side effects was observed.

Clinical observation of conformal radiotherapy with topotecan che-motherapy on patients with platinum-resistant recurrent ovarian cancer / 中国肿瘤临床

Objective: This study aims to observe the efficacy and toxicity of three-dimensional conformal radiotherapy (3DCRT) combined with weekly topotecan hydrochloride (Top-Hyd) chemotherapy on patients with platinum-resistant recurrent ovarian cancer. Methods: Medical data of 42 patients with platinum-resistant recurrent ovarian cancer between June 2008 and June 2011 were retrospectively reviewed. OAOf these 42 patients, 22 underwent 3DCRT combined with weekly Top–Hyd chemotherapy, whereas the remaining 20 underwent simple chemotherapy (SCT). Doses from 45 Gy to 65 Gy were planned to deliver fractions ranging from 1.8 Gy to 2 Gy to patient abdomen and pelvis. Top–Hyd (4 mg/m2) was aintravenously administered 1, 8, and 15 days from radiotherapy, with a cycle of 28 days. Results: By December 31, 2011, the median follow-up time for the 3DRT group was 18.5 months, whereas that for the SCT group was 10.8 months . The total response rate and the clinical beneficial rate were significantly higher in the 3DCRT group than in the SCT group (total response rate, 42.1% vs. 11.1%; clinical beneficial rate, 68.4% vs 22.2% at P0.05). Conclusion: The combined 3DCRT treatment and Top-Hyd chemotherapy results in enhanced response and tolerable toxicity compared with SCT in patients with recurrent ovarian cancer infiltrating the pelvic and retroperitoneal lymph node metastasis. So, it may be the salvage regimen for recurrent ovarian cancer and provide a new therapeutic option for the consolidation treatment of advanced ovarian carcinoma.

Outcomes of advanced and recurrent cervical cancer treated with cisplatin and generic topotecan: retrospective analysis in a tertiary care hospital in Thailand / 부인종양

OBJECTIVE: Retrospective evaluation of the outcome of stage IVB, recurrent or persistent cervical cancer treated with cisplatin and generic topotecan (CT) in a tertiary care hospital in Thailand. METHODS: The medical records of patients treated with CT regimen at Chiang Mai University Hospital between January 2005 and December 2007 were reviewed and analyzed. The treatment protocol consisted of IV topotecan 0.75 mg/m2 on days 1, 2, and 3; combined with cisplatin 50 mg/m2 IV on day 1 and repeated every 21 days until progression or unacceptable toxicity for a maximum of 6 cycles. The outcomes were evaluated based on the response rate, progression free survival (PFS), and overall survival (OS) by using the World Health Organization criteria. The adverse effects of the treatments were also determined. RESULTS: Twenty-one cervical cancer patients received the CT regimen. The tumor response rate was 28.6%. The median PFS and OS was 4 and 11 months, respectively. With 87 cycles of chemotherapy, the most common grade 3 & 4 hematologic toxicity was neutropenia (57.9%). CONCLUSION: Advanced and recurrent cervical cancer patients treated with cisplatin and generic topotecan had a favorable outcome with manageable toxicity.

Inhibition and radiosensitization of Topotecan,Cisplatin and Taxol on cervical cancer cell line HeLa / 上海交通大学学报（医学版）

Objective To investigate the inhibition and radiosensitization effects of Topotecan(TPT)on cervical cancer cell line HeLa,and make comparison with Cisplatin(DDP)and Taxol(TAX).Methods The effects of TPT,DDP and TAX on proliferation of cervical cancer cell line HeLa were evaluated by MTT assay.The radiosensitization effects of TPT,DDP and TAX on HeLa cells were detected by clone formation assay,and the sensitization enhancement ratios of TPT,DDP and TAX were calculated.Results The IC_(50) of TPT at different reaction time(24 h,48 h and 72 h)were 8.0μg/mL,2.6 μg/mL and 0.8 μg/mL,respectively,those of DDP were 2.4 μg/mL,0.7 μg/mL and 0.1μg/mL,respectively,and those of TAX were 0.3 μg/mL,0.1μg/mL and 0.0 μg/mL, respectively.The apoptosis rates of tumor cells treated by radiosensitization were significantly higher than those of tumor cells treated by single radiotherapy or single chemotherapy (P<0.05).The sensitization enhancement ratios of TPT at 24 h and 48 h were 1.167 and 1.344,respectively,those of DDP were 1.314 and 1.538,respectively,and those of TAX were 1.076 and 1.316,respectively.Conclusio TPT,DDP and TAX have significant inhibition effects on cervical cancer cell line HeLa, which are time-dependant and dose-dependant. Besides,TPT,DDP and TAX have radiosensitizing effects, with DDP being the strongest and TAX being the weakest.

Study on treatment of H22 liver cancer using 10-HCPT-Ioaded microbubbles and ultrasound-targeted destruction / 中华超声影像学杂志

Objective To prepare lipid-coated ultrasound microbubbles containing 10-HCPT(HLM) and explore the antitumor effects on mice xenografed H22 solid tumor using the technique of ultrasound-mediated HLM destruction. Methods Sixty-four tumor-bearing mice were radomly divided into A and B groups. Each group was divided into four groups again and administered respectively by tail vein with HI.M, non-drug-loaded microbubbles,10-HCPT and saline once a day. Ultrasound irradiation was applied on the tumor sites immediately after injection. After 7 days of consecutive treatment, all mice in group A were sacrificed and the tumors were harvested to measure weights. The tumor inhibition rate was calculated by weights. The tumor microvessel density (MVD) was detected by immunohistochemical staining. The tumor growth curve was depicted according to volumes. The survival time of mice in group B was recorded. Results The tumor inhibition rate was the highest in HLM group while this group's MVD was the lowest. Survival time in HLM group and 10-HCPT group were obviously longer compared with the control group,while no statistic difference was observed between the two groups. There was no statistic difference between the group of non-drug-loaded microbubbles and the control group. Conclusions Ultrasound irradiation mediates HLM destruction so that the drug is released from the vihicles at the same time, which can significantly enhance the tumor inhibition effect of 10-HCPT on the H22 tumor. This technique is expected to be adopted as a novel tool for liver cancer chemotherapy.

Notch3 siRNA enhances chemosensitivity of colon cancer cells to topotecan / 中国肿瘤生物治疗杂志

Objective: To elucidate the relationship between Notch3 expression and chemosensitivity of human colon carcinoma cell line SW620 to topotecan. Methods: Notch3 siRNA was transfected into SW620 cells, and the expression of Notch3 in SW620 cells was examined by Western blotting. After transfected with Notch3 siRNA for different time peri-ods, SW620 cells were further treated with topotecan, and the proliferation of SW620 cells was detected by MTT assay; the apoptosis of SW620 cells was detected by Hoechst 33342 staining and flow cytometry. Caspase-3 activation in SW620 cells was examined by caspase-3 activation kit. Results: Notch3 siRNA transfection remarkably inhibited Notch3 protein expression in SW620 cells. The IC_(50) of topotecan in Notch3 siRNA-transfected group was significantly decreased compared with that in the Ctrl siRNA group (P <0.05). Silence of Notch3 expression in SW620 cells by Notch3 siRNA remarkably promoted apoptosis (P < 0.05) and caspase-3 activation (P < 0.05) of SW620 cells induced by topotecan. Conclusion: Notch3 down-regulation by siRNA in SW620 cells can enhance the chemosensitivity cells to topotecan.

Acute Respiratory Distress Syndrome after Topotecan Therapy in a Patient with Small Cell Lung Cancer / 결핵및호흡기질환

Small cell lung cancer is characterized by an aggressive clinical course and a high tendency for early dissemination in spite of a good chemotherapy response. Topotecan is a topoisomerase I inhibitor, and it is used as second-line treatment for small cell lung cancer. The reported dose-limiting adverse reactions to topotecan are mainly hematologic. Yet pulmonary toxicity associated with topotecan is known to be rare. We report here on a case that showed the development of acute respiratory distress syndrome during the 3rd cycle of topotecan chemotherapy in a patient with small cell lung cancer. He developed dyspnea and respiratory failure, and the chest CT scan revealed diffuse ground-glass opacity that was probably due to chemotherapy-related pulmonary toxicity. He finally died of acute respiratory distress syndrome.

The efficacy and toxicity of topotecan in combination with platinum in patients with recurrent epithelial ovarian cancer and primary peritoneal carcinomatosis / 대한산부인과학회지

OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicity of topotecan, camptothecin analogue topoisomerase I inhibitor, as the combination therapy with platinum in patients with recurrent epithelial ovarian carcinoma and primary peritoneal carcinomatosis. METHOD: In this study, patients who were treated with topotecan between January 2000 and June 2007 at Asan Medical Center, Seoul, Korea were reviewed. Fifty-one patients with recurrent ovarian carcinoma and peritoneal carcinomatosis were included. These patients' data were analyzed by review of medical records and pathologic and laboratory reports retrospectively. Response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria for patients with measurable disease and CA-125 response criteria for patients with non-measurable disease. The toxicities were evaluated according to NCI CTC (Common Toxicity Criteria) version 3.0. RESULTS: The mean age of patients was 53.4 years (ranged between 37 and 69). Forty-four patients had been evaluated by RECIST criteria. The overall response rate was 22.8% (10/44). Platinum-sensitive patients showed more favorable response rate (26.9%) than platinum-resistant patients (16.7%), however, it was not significant statistically (p=0.425). Platinum-sensitive group had significantly longer response duration (12.14 vs. 3.33 months, p=0.022) and time-to-progression (11.34 vs. 7.33 months, p=0.042) than platinum-resistant group. Heavily pretreated group, three or more prior regimens were used, had no significant differences from another group. The most common adverse effect of topotecan in combination with platinum was hematologic toxicity; grade 3/4 neutropenia was 30.6%, anemia was 42.7%, and thrombocytopenia was 8.37% in total 265 cycles of chemotherapy, however, it was tolerable. CONCLUSION: Topotecan in combination with platinum is considered as effective regimen with acceptable toxicity in treating recurrent epithelial ovarian carcinoma and primary peritoneal carcinomatosis who have failed previous treatment with platinum-containing chemotherapy.

Inhibitory cells proliferation and induce cells apoptosis by TPT on HL-60 cell by c-myc / 白血病·淋巴瘤

Objective The effects of TPT on the induction of apoptosis of leukemia cells and the regulation of c-myc in mRNA and protein level. Methods RT-PCR method was adopted to examine the expressions of the genes and immune histochemistry for the proteins of c-myc in HL-60 cells treated with TPT of optimal concentration and time. Results After HL-60 cells by TPT of 0.15 μmol/L for 12 h, the expression of c-myc mRNA decreased markedly assayed by RT-PCR. There was a significant difference between the TPT group and the control group(0.17±0.03 vs 1.11±0.25, P <0.05), expressive c-myc protein decreased assayed by evidently immunohistochemistry. The percentage of positive cells expressing c-myc protein was a significant difference between the TPT treated group and the control group (19.67 % vs 68.33 %, P<0.05). Conclusion TPT down-regulates endogenic c-myc mRNA and c-myc protein in HL-60 cells.

A clinical study comparing topotecan plus carboplatin versus etoposide plus carboplatin for previ-ously untreated small cell lung cancer / 中国医师进修杂志

Objective To assess the efficacy and toxicity of topoteean hydllochloride plus carbo-platin(TC)versus etoposide plus carboplatin(CE)in patients for previously untreated small cell lung cancer (SCLC).Methods Sixty-nine patients with previously untreated SCLC,TC group(34 eases)were treated with topotecan 1 mg/m2 from day 1 to day 5 and carboplatin 300 mg/m2on day 1.CE group(35 cases)were treated with etoposide 100 mg/d from day 1 to day 5 and carboplatin 300 mg/m2 on day 1.Treatment was repeated every 3 weeks.The efficacy and toxicity were ev Mumed in patients who received two cvcles of chemotherapy.ResMN The total effective rate Was 76.5%in TC group and 71.4%in CE group(P＞0.05). The progression-free survival interval was 4.1 months in TC group and 2.6 months in CE group(P＜0.05). There was no significant difference in the most common toxieities between two groups(P＞0.05).Conclusion Compared with etoposide plus carboplatin,topotecan plus carboplatin has similar total effective rate,and in- different toxieities,and the longer progression-free survival interval,so it is a safe and effective first-line treatment for SCLC.

Clinical study of the effect of topotecan in combination with chemotherapy on relapsed and refractory acute myelogenous leukemia / 重庆医科大学学报

Objective:To evaluate the antileukemic activity and side effects of topotecan in patients with refractory and relapsed acute myelogenous leukemia(AML).Method:12cases of refractory and relapsed AML were treated with topotecan combined with chemotherapy,8 accepted 1 course,and the others accepted 2 courses.Result:4 patients achieved complete remission.3 had partial remission.The total response rate was 58%.The main side effect was myelosuppression.Conclusion:The topotecan-based induction therapy has antileukemic effect in some patients with refractory and relapsed AML.

Combination chemotherapy with topotecan and vincristine for patients with refractory or recurrent small cell lung cancer / 대한내과학회지

BACKGROUDN: Small cell lung cancer (SCLC) is a chemotherapy-sensitive tumor. However, the duration of response is usually short and most patients experience relapses. Topotecan is commonly used for treatment of these patients. Nevertheless, the response rate of topotecan as a single regimen is only about 20% and the resulting severe myelosuppression is troublesome. Vincristine is also an active agent, and it does not compromise the marrow function. In this background, we evaluated the efficacy and toxicities of topotecan and vincristine combination chemotherapy. METHODS: Patients with pathologically confirmed SCLC refractory to or recurrent after platinum-based chemotherapy were eligible for this study. The treatment regimen was as follows; topotecan 1.5 mg/m2/day IV bolus on day 1, 2 and 3 and vincristine 1.5 mg/m2 (maximum 2 mg on day 1 (on every cycle)) and day 2 (on odd cycles only). This regimen was repeated every 3 weeks. The efficacy was evaluated in terms of response rate, time to progression and overall survival duration. The toxicities were assessed according to NCI-CTC version 3.0. RESULTS: A total of 19 patients were entered into this study. The median age was 63 years (range 43-85 years). Partial response was obtained for 3 patients (response rate 15.8%, 95% CI: 0-32.5%). The median time to progression and survival duration was 51 days and 199 days, respectively. For a total of 52 cycles of treatment, grade 3 or 4 neutropenia and thrombocytopenia were observed in 25.0% and 11.5% of the patients, respectively. Grade 2 neurotoxicities were observed in 15.4% of the patients. There was no treatment-related mortality. CONCLUSIONS: The topotecan and vincritine combination is active and safe for patients with recurrence or refractory SCLC. However, the benefit of adding vincristine to topotecan needs to be confirmed in further studies.

In vivo study of radiosensitization by Topotecan on nasopharyngeal carcinoma / 中国耳鼻咽喉头颈外科

OBJECTIVE To study the radiose-nsitization by Topotecan on human nasopharyngeal carcinoma in nude mice. METHODS ①To study the maximum tolerance dose of TPT and detect the effective rate of TPT and RT on nude mice. ② Plan of radiosensitization practice:53 nude mice xenografts were distributed to 5 groups:RT 20 Gy group,RT 40 Gy group,TPT 12.5 mg/kg group,TPT 12.5 mg/kg+RT 20 Gy group and the controlgroup. After treatment,the volume of tumors were measured every 3 days in order to value the effective rate [complete remission(CR) + partial remission(PR) ]and regrowth delay time(TGD) and to fit the growth curve. RESULTS This study showed that the effective rates had significant difference among RT20 Gy+TPT 12.5 mg/kg group,RT20 Gy group and TPT12.5 mg/kg group,while that of RT20 Gy +TPT 12.5 mg/kg group and RT40 Gy group had no statistical difference. SER reached to 1.34. CONCLUSION Topotecan has been shown a radiosensitizing effect on human nasopharyngeal carcinoma in vivo.

Comparison of efficacy and toxicity profile between intraperitoneal and intravenous topotecan in human ovarian cancer xenografts / 北京大学学报(医学版)

Objective:To compare the therapeutic and toxic profile of topotecan given intraperitoneally with intravenously in human ovarian cancer xenografted into athymic nude mice.Methods: Eighty female Balb-c/nu-nu mice were randomized assigned into eight groups (n=10). Xeneografts resulted from intramesentery injection of cultured human ovarian cancer cells SKOV3 in athymic mice. Onset of intraperitoneal treatment with either topotecan or cisplatin (7.5 mg/kg) was on day 7. Animals scheduled for topotecan i.p. received intraperitoneal application of topotecan (1.5 mg/kg×2, 3.0 mg/kg×2, 6.0 mg/kg×2 or 10.0 mg/kg×1). Animals scheduled for topotecan i.v. received intravenous administration of topotecan (6.0 mg/kg×2 or 10.0 mg/kg×1). Two weeks after drug application animals were killed. Tumor growth inhibition were assessed and compared with untreated mice and cisplatin intraperitoneally administered mice. Acute toxicity was determined by loss of body weight. Cell cycle division and apoptosis after drug administration was determined by flow cytometric analysis.Results: In a panel of ten tumour xenografts, intraperitoneal topotecan was significantly more effective than intravenous administration. The toxicity profile suggested a better tolerability in terms of weight loss after intraperitoneal administration than cisplatin control. Topotecan 10.0 mg/kg i.p. per day (1 day) schedule was an optimal treatment for ovarian cancer and well tolerated by mice with no signs of acute toxicity. Topotecan and cisplatin induce cells G0-G1 arrest and apparent apoptosis. No significant difference among mice treated with topotecan intraperitoneally or intravenously or cisplatin was observed in term of apoptosis and cell cycle perturbation.Conclusion:The results may have implications for the future design of clinical studies on intraperitoneal application of topotecan. It suggests that apoptosis and cell cycle perturbation play an limited role in the mechanism of topotecan administration.

The role of topotecan as second-line chemotherapy in patients with recurrent epithelial ovarian cancer / 대한산부인과학회지

OBJECTIVE: Topotecan has recently been used as a second-line agent in treatment of advanced ovarian cancer. The aim of the study was to evaluate the response rate and toxicities of topotecan in patients with recurrent epithelial ovarian cancer who had been treated with platinum-containing chemotherapy. METHODS: A retrospective review of all cases of recurrent ovarian cancer treated with topotecan was done. Response was evaluated using the clinical examination, CA-125 level and radiologic reports (CT, MRI) according to RECIST criteria. The toxicities were evaluated according to GOG criteria. RESULTS: Between 1998 and 2004, 57 patients were treated with topotecan for recurrent epithelial ovarian cancer. The response rate in platinum-sensitive group was 30.8% (4/13) and the response rate in platinum-resistant group was 15.9% (7/44). The response rate in topotecan alone therapy group was 8.0% (2/25), and the response rate in topotecan plus platinum combination therapy group was 28.1% (9/32). However, topotecan plus platinum combination therapy did not demonstrate a statistically significant trend toward greater median survival than topotecan alone therapy (19.2 month versus 17.2 month, P=0.82). Neutropenia above grade 3 was noted in 70%, and anemia above grade 3 in 36.8%, and thrombocytopenia above grade 3 in 47.3%. Although most severe toxicities were due to bone marrow suppression, they were adequately managed by supportive care. CONCLUSION: The results suggest that topotecan has moderate activity in the recurrent epithelial ovarian cancer who have failed previous treatment with platinum-containing chemotherapy. The response of topotecan plus platinum combination therapy was better than topotecan alone and the potential of other combination regimen deserves further evaluations.