Background: Intravitreal chemotherapy has been an effective addition in treating vitreous seeding in retinoblastoma. However, it was only in 2020 that it was used in the Philippines. There is no literature on its use in multiple Filipino retinoblastoma patients. Objectives: To describe the clinical course of the four patients who are the first to undergo intravitreal chemotherapy for vitreous seeding of retinoblastoma in the Philippine tertiary hospital. Methods: A case series of four eyes of four patients with retinoblastoma who underwent intravitreous injection of melphalan and topotecan for vitreous seeding at the Department of Ophthalmology and Visual Sciences of a Philippine tertiary hospital. Results: Two eyes, with International Intraocular Retinoblastoma Classification (IIRC) Group C with vitreous seeding, responded well to intravitreous melphalan and topotecan. One eye had recurrent vitreous seeding despite 10 intravitreal injections. One eye with IIRC Group E, did not respond to intravitreous chemotherapy and was eventually enucleated. This is the first case series on the local use of intravitreous chemotherapy in the country for vitreous seeding in retinoblastoma. The control of 50% achieved in this case series is lower than in other series due to longer treatment interval from poor follow-up and the presence of advanced disease. Conclusion The use of intravitreous melphalan and topotecan can be an effective adjuvant for systemic chemotherapy in controlling vitreous seeding in eyes with IIRC Group C. It is not effective in controlling IIRC Group E disease.
intravitreous ; melphalan ; topotecan ; retinoblastoma ; Philippines

Ovarian cancer has the highest mortality rate among gynecologic malignancies in developed countries. Most women present with advanced disease and require a combination of surgery and chemotherapy. One patient presented with recurrent ovarian cancer was initially treated with taxol and platinum-based compounds. Although response to these agents occurred, tumor progression was evident by elevated CA 125 levels and CT findings after a period of 4 months. This patient was then treated with topotecan and exhibited a response and stopped therapy. Topotecan exhibited activity in this patient with ovarian cancer resistent to both platinum and paclitaxel. We report a case of advanced ovarian cancer which was treated with topotecan after taxol-cisplatin treatment failed.
Developed Countries ; Drug Therapy ; Female ; Humans ; Mortality ; Ovarian Neoplasms* ; Paclitaxel ; Platinum ; Topotecan*

OBJECTIVE: Theoretically, chemotherapy sensitivity and resistance assays help to predict which sensitive agent will be effective for patients. Due to low correlation between in vitro assay results and in vivo responses, chemosensitivity test is not generally applied in actual clinical practices. The aim of this study is to evaluate the influence of cell cycle in the course of cell culture stage on chemosensitivity test as a disturbing factor. METHODS:After synchronization at G0, we conducted experiments on SKOV-3 cell line according to determined cell cycle span (G0, G0/G1, S, G2/M) with MTT (methylthiazolyl-diphenyl- tetrazolium bromide) chemosensitivity test. We evaluated the sensitivity changes of six chemotherapeutic agents (5-FU, Etoposide, Cisplatin, Topotecan, Paclitaxel, Doxorubicin) in each phase at target times. RESULTS: Each phase represented the various results of MTT sensitivity on six chemotherapeutic agents. The variation of sensitivity between experimental (cell cycle synchronized culture) group and reference (conventional culture) group was 21.3+/-5.1 (mean+/-.D)%. CONCLUSION: The cells in the each phase of cell cycle represent different levels of sensitivity to the same chemotherapeutic agent. The required cell culture stage of chemosensitivity test can blur the true candidate agent. This finding can be regarded as one of the reasons of mismatch between in vitro chemosensitivity and in vivo response of candidate chemotherapeutic agents.
Cell Culture Techniques ; Cell Cycle ; Cell Line ; Cisplatin ; Etoposide ; Humans ; Ovarian Neoplasms ; Paclitaxel ; Topotecan

OBJECTIVE: Theoretically, chemotherapy sensitivity and resistance assays help to predict which sensitive agent will be effective for patients. Due to low correlation between in vitro assay results and in vivo responses, chemosensitivity test is not generally applied in actual clinical practices. The aim of this study is to evaluate the influence of cell cycle in the course of cell culture stage on chemosensitivity test as a disturbing factor. METHODS:After synchronization at G0, we conducted experiments on SKOV-3 cell line according to determined cell cycle span (G0, G0/G1, S, G2/M) with MTT (methylthiazolyl-diphenyl- tetrazolium bromide) chemosensitivity test. We evaluated the sensitivity changes of six chemotherapeutic agents (5-FU, Etoposide, Cisplatin, Topotecan, Paclitaxel, Doxorubicin) in each phase at target times. RESULTS: Each phase represented the various results of MTT sensitivity on six chemotherapeutic agents. The variation of sensitivity between experimental (cell cycle synchronized culture) group and reference (conventional culture) group was 21.3+/-5.1 (mean+/-.D)%. CONCLUSION: The cells in the each phase of cell cycle represent different levels of sensitivity to the same chemotherapeutic agent. The required cell culture stage of chemosensitivity test can blur the true candidate agent. This finding can be regarded as one of the reasons of mismatch between in vitro chemosensitivity and in vivo response of candidate chemotherapeutic agents.
Cell Culture Techniques ; Cell Cycle ; Cell Line ; Cisplatin ; Etoposide ; Humans ; Ovarian Neoplasms ; Paclitaxel ; Topotecan

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.
Anemia ; Bone Marrow ; Drug Therapy* ; Humans ; Neutropenia ; Ovarian Neoplasms* ; Platinum ; Retrospective Studies ; Thrombocytopenia ; Topotecan*

OBJECTIVE: The aim of this study was to evaluate Topotecan-, Cisplatin- and Taxol-induced apoptosis in five human ovarian cell lines as a measure of chemosensitiviy and relationship between apoptosis and p53 and bcl-2 gene expression. METHODS: In this study, the author is presenting data on apoptosis induced by Topotecan, Cisplatin and Taxol in five ovarian cancer cell lines, and represent different levels of sensitivities to Topotecan, Cisplatin and Taxol. This study also includes the interaction of these chemotherapeutic agents on ovarian cancer cell lines with respect to the apoptosis and cytotoxicity assay as a quantitative measure of the efficiency of killing. Presence of the p53 and bcl-2 gene product were examined by western blotting. RESULTS: The five cell lines represent various sensitivities to Topotecan, Cisplatin, Taxol (LD50 range of Topotecan, 30~1000 ng/ml; Cisplatin, 3~10 microgram/ml, Taxol 5~1000 nm). SKOV-3 represent a resistant cell line which was 2~30 times resistant to Topotecan, 3 times resistant to Cisplatin, and 2~200 times resistant to Taxol when compared to others. Demonstration of apoptosis correlated with the sensitivity of the cell lines to Topotecan, Cisplatin and Taxol for SNU-840 and OVCAR-3. DNA fragmentation of OVCAR-3 was uniformly present when treated with Topotecan, Cisplatin and Taxol, 24 or 48 hours. When sequencing experimetns were performed with correlated with cytotoxicity assays, except in SNU-251 cells where no signigicant difference was observed in different interactions of Topotecan, Cisplatin and Taxol. Pretreatment with Topotecan, Cisplatin at a 24 hour interval resulted in enhanced cytotoxicity. Quantitation of the fragmented DNA correlated with that seen on gel electrophoresis. CONCLUSION: The study indicate that the ability to achieve significant cytotoxicity by Topotecan, Cisplatin and Taxol may be related to the induction of apoptosis rather than necrosis. However, outcome of these treatments depend on cellular and genetic characheristics.
Apoptosis* ; Blotting, Western ; Cell Line* ; Cisplatin* ; DNA ; DNA Fragmentation ; Electrophoresis ; Genes, bcl-2 ; Homicide ; Humans ; Necrosis ; Ovarian Neoplasms* ; Paclitaxel* ; Topotecan*

PURPOSE: Chemotherapy is the treatment of choice for small-cell lung cancer (SCLC). Despite the high response rates with first-line therapy, most patients eventually experience disease progression, and finally become candidates for second-line therapy. Topotecan is the only single agent currently approved in the United States for the treatment of a recurrent disease. The aim of this study was to evaluate its efficacy in patients with of previously treated, but relapsed and refractory, SCLC. MATERIALS AND METHODS: Twenty-five patients, who had taken topotecan as a second-line therapy, between March 1999 and October 2002, were reviewed. The patients were divided into two groups: (1) One group were the patients that had failed the first-line treatment within 3 months from end of the chemotherapy (refractory group, RG); and (2) the other group were those that responded to the first-line treatment, but who progressed 3 months after the end of the chemotherapy (sensitive group, SG). Topotecan was administered, intravenously, at a dose of 1.5 mg/m2, within 30 minutes, for five consecutive days every 3 weeks. RESULTS: There was only one partial response in the SG (3.8%), but there were 9 stable diseases, 4 in the SG and 5 in the RG; 15.4 and 19.2%, respectively. The median survivals were 6.9 and 5.2 months in SG and RG, respectively (p=0.162). There were ninety-nine chemotherapy cycles. The toxicities were mainly hematological. There were 26 incidences of Grades III and IV neutropenia, and the non hematological toxicities were mild. CONCLUSION: It was concluded that topotecan is not so effective in the treatment of patients with relapsed and refractory SCLC, despite its predictable and manageable toxicity. The incorporation of topotecan in combination chemotherapy regimens for treatment of SCLC is now warranted.
Disease Progression ; Drug Therapy ; Drug Therapy, Combination ; Humans ; Incidence ; Lung Neoplasms* ; Lung* ; Neutropenia ; Retrospective Studies* ; Topotecan* ; United States

OBJECTIVE: Taxol (Bristol-Myers Squibb)(paclitaxel) has been shown to be a potent inhibitor of cell growth for a variety of tumors. The aim of this study was to evaluate the interaction of five different combinations of drugs: taxol and cisplatin, topotecan, actinomycin D, methotrexate, and etoposide in two established choriocarcinoma cancer cell lines to identify potential synergistic combinations of chemotherapy for patients with choriocarcinoma. METHODS: Six antitumor drugs were tested for synergism and antagonism in combination studies using human choriocarcinoma cell lines, JAR and BeWo. Cytotoxic effects were determined by 3-(4,5- dimethylthiazol-2-ly)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Synergic interactions were determined by the median effect principle in which Combination lndex (CI) of less than one suggest a synergic interaction. RESULTS: Proliferation of JAR and BeWo cells was inhibited by taxol and 2.7 to 86 nmol/L was needed to achieve 50% growth reduction. Combination effect of taxol/cisplatin (fixed ratio of 8 nM: 0.8 ug and 333 nM: 0.8 ug) and taxol/actinomycin-D (fixed ratio of 8 nM: 0.17 nM and 300 nM: 0.003 nM) in JAR and BeWo cell lines showed a synergistic effect at the intermediate and high level of cytotoxicity in both cell lines. Combination effect of taxol/topotecan at all fixed ratio of 8 nM: 1.7 ug showed a synergistic effect at the intermediate and high level of cytotoxicity in JAR cell line. Combination effect of taxol/etoposide at fixed ratio of 8 nM: 0.83 ug and 333 nM: 1.67 ug in JAR and BeWo cell lines showed an antagonistic effect at all level of cytotoxicity in both cell lines. CONCLUSION: These results suggest that taxol is synergistic with cisplatin, actinomycin-D in both cell lines tested and synergistic with topotecan, methotrexate in one cell line. However the most active drug against trophoblastic disease, etoposide, was antagonistic with taxol in both cell lines. Clinical trials using taxol/ cisplatin or taxol/topotecan combination are warranted to determine whether there is a survival advantage in refractory choriocarcinoma or high risk group and a survival can be achieved with taxol in combination with these drugs.
Antineoplastic Agents* ; Cell Line* ; Choriocarcinoma* ; Cisplatin ; Dactinomycin ; Drug Therapy ; Etoposide ; Female ; Humans ; Methotrexate ; Paclitaxel* ; Pregnancy ; Topotecan ; Trophoblasts

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.
Bone Marrow ; Drug Therapy ; Drug Therapy, Combination* ; Humans ; Mortality ; Neutropenia ; Recurrence ; Small Cell Lung Carcinoma* ; Thrombocytopenia ; Topotecan* ; Vincristine*

OBJECTIVE: In an effort to develop a more effective therapeutic strategy for ovarian cancer, we examined whether the restoration of the wild-type p53 gene can enhance the therapeutic effect of chemotherapy. METHODS: In this study, Ov-ca-2774 cells, which are known to have p53 point mutation and cisplatin-resistance, were selected and currently used chemotherapeutic agents including cisplatin, carboplatin, paclitaxel, etoposide, topotecan, and doxorubicin were added concurrently or sequentially with adenovirus-mediated p53 gene transfer (Ad5CMV-p53). RESULTS: Transfer of the wild-type p53 cDNA gene into Ov-ca-2774 cells showed 55% cell killing in vitro at a multiplicity of infection (MOI) of 40. Although the combination of carboplatin or paclitaxel followed by p53 gene transfer with an interval of 48 h manifested no enhanced cell killing compared with cells infected with Ad5CMV-p53 alone, the other combinations of chemotherapeutic agents and p53 gene transfer resulted in 15% to 37% further cell killing (P<0.05). Furthermore, p53 gene transfer followed by doxorubicin with an interval of 24 h and concurrent combination of etoposide with p53 gene transfer showed significant difference in cell killing in contrast to the other combination strategies in the respective chemotherapeutic agent exposure groups (P<0.05). CONCLUSION: Our data demonstrated that combination of p53 gene transfer and chemotherapeutic agents had higher cell killing than either of these two modality alone.
Carboplatin ; Cisplatin ; DNA, Complementary ; Doxorubicin ; Drug Therapy* ; Etoposide ; Genes, p53 ; Homicide ; Humans* ; Ovarian Neoplasms* ; Paclitaxel ; Point Mutation ; Topotecan