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Objective To determine the influence of abiraterone acetate (AA) on neuroendocrine differentiation (NED) in metastatic castration-resistant prostate cancer (mCRPC) and the prognostic predicting value of the serum NED markers in mCRPC patients treated with AA.Methods We conducted an analysis in 115 chemotherapy-naive mCRPC patients who were treated with chemotherapy in Renji hospital from 2013 to 2017.The median age was 70,ranged from 65 to 76 years old.The median CgA,NSE and PSA levels were 101.1 ng/ml (78.5-150.0 ng/ml),13.4 ng/ml (10.5-17.6 ng/ml) and 38.8 ng/ml (11.2-123.2 ng/ml),respectively.Among them,48 cases were classified as the group without AA treatment.The other 67 cases were classified as group after AA failure.In group without AA treatment,the median CgA,NSE and PSA levels were 109.1 ng/ml(80-151.5 ng/ml);13.8 ng/ml(10.8-18.2 ng/ml) and 39.2 ng/ml (8.6-200 ng/ml),respectively.In group after AA failure,the median CgA,NSE and PSA levels were 105.4 ng/ml(78.8-175.5 ng/ml),13.8 ng/ml(10.8-17.6 ng/ml) and 39.0 ng/ml(8.4-219.8 ng/ml),respectively.In the group with serial evaluation of NED markers during AA treatment,the median serum CgA,NSE levels at baseline were 115.9 ng/ml(90.1-201.5 ng/ml),13.3 ng/ml (10.4-18.1 ng/ml),respectively.The endpoints were PSA PFS(progression-free survival) and radiographic PFS (rPFS).Results In 34 patients with serial evaluation,serum NED markers level in 19 patients increased after the failure of AA treatment.Median serum CgA and NSE levels were 115.9 ng/ml(90.1-201.5 ng/ml)and 13.25 ng/ml (10.37-18.14 ng/ml) at baseline.Median serum CgA and NSE levels were 129.6ng/ml (75.5-230.5 ng/ml) and 14.7 ng/ml (11.8-19.1 ng/ml) after 6 months treatment,respectively.The median serum CgA and NSE levels were 130.4 ng/ml (95.7-205.7 ng/ml) and 15.2 ng/ml(12.4-18.7 ng/ml) at the time of failure of AA treatment,respectively.There was no significant difference of NED markers between baseline and failure of AA treatment (P =0.243).In logistic univariate analysis,AA treatment and its duration were not independent factors influencing NED(P =0.30;P =0.52).Compared with the NED markers elevation group in the first 6 months of AA treatment and baseline supranormal NED markers group,the NED markers decline group(PSA PFS(17.1 vs.10.4 months,P ＜ 0.001) and rPFS (17.0 vs.10.4 months,P =0.003)) and baseline normal NED markers group(PSA PFS(14.1 vs.9.5 months,P =0.001) and rPFS(16.4 vs.10.5 months,P ＜ 0.001)) has a longer median PSA PFS and rPFS respectively.In multivariate Cox analysis,baseline NED markers level and NED markers variation during the first 6 months of AA treatment remained significant predictors of rPFS(P ＜ 0.05),and PSA-PFS (P ＜ 0.05).Conclusions We found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment,and AA might not significantly lead to progression of NED of mCRPC in general.Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.Serum NED markers elevation during the first 6 months of AA treatment and elevated baseline NED markers levels indicated poor prognosis in mCRPC treated with AA.
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BACKGROUND: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. Irinotecan also can act as a potential radiation sensitizer along with cisplatin. To evaluate efficacy and toxicity of irinotecan plus cisplatin (IP) with concurrent thoracic radiotherapy, we conducted a phase II study of IP followed by concurrent IP plus hyperfractionated thoracic radiotherapy in patients with previously untreated limited-stage small-cell lung cancer. METHODS: Twenty-four patients with previously untreated small-cell lung cancer were enrolled onto the study since November 2004. Irinotecan 60 mg/m2 was administered intravenously on days 1 and 8 in combination with cisplatin 60 mg/m2 on day1 every 21 days. From the first day of third cycle, twice-daily thoracic irradiation (total 45 Gy) was given. Prophylactic cranial irradiation was given to the patients who showed complete remission after concurrent chemoradiotherapy. Restaging was done after second and sixth cycle with chest CT and/or bronchosocpy. RESULTS: Up to November 2004, 19 patients were assessable. The median follow-up time was 12.5 months. A total of 99 cycles (median 5.2 cycles per patient) were administered. The actual dose intensity values were cisplatin 19.6 mg/m2/week and irinotecan 38.2 mg/m2/week. Among the 19 patients, the objective response rate was 95% (19 patients), with 9 patients (47%) having a complete response (CR). The major grade 3/4 hematological toxicities were neutropenia (35% of cycles), anemia (7% of cycles), thrombocytopenia (7% of cycles). Febrile neutropenia was 4% of cycles. The predominant grade 3/4 non-hematological toxicities was diarrhea (5% of cycles). Toxicities was not significantly different with concurrent administration of irinotecan and cisplatin with radiotherapy, except grade 3/4 radiation esophagitis (10% of patients). No treatment-related deaths were observed. The 1-year and 2-year survival rate of eligible patients was 89% (16/18) and 47% (9/18), respectively. CONCLUSION: Three-week schedule of irinotecan plus cisplatin followed by concurrent IP plus hyperfractionated thoracic radiotherapy is an effective treatment for limited disease small-cell lung cancer, with acceptable toxicity.
Subject(s)
Humans , Anemia , Appointments and Schedules , Chemoradiotherapy , Cisplatin , Cranial Irradiation , Diarrhea , DNA Topoisomerases, Type I , Drug Therapy , Esophagitis , Febrile Neutropenia , Follow-Up Studies , Lung Neoplasms , Neutropenia , Radiotherapy , Small Cell Lung Carcinoma , Survival Rate , Thrombocytopenia , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. Irinotecan also can act as a potential radiation sensitizer along with cisplatin. To evaluate efficacy and toxicity of irinotecan plus cisplatin (IP) with concurrent thoracic radiotherapy, we conducted a phase II study of IP followed by concurrent IP plus hyperfractionated thoracic radiotherapy in patients with previously untreated limited-stage small-cell lung cancer. METHODS: Twenty-four patients with previously untreated small-cell lung cancer were enrolled onto the study since November 2004. Irinotecan 60 mg/m2 was administered intravenously on days 1 and 8 in combination with cisplatin 60 mg/m2 on day1 every 21 days. From the first day of third cycle, twice-daily thoracic irradiation (total 45 Gy) was given. Prophylactic cranial irradiation was given to the patients who showed complete remission after concurrent chemoradiotherapy. Restaging was done after second and sixth cycle with chest CT and/or bronchosocpy. RESULTS: Up to November 2004, 19 patients were assessable. The median follow-up time was 12.5 months. A total of 99 cycles (median 5.2 cycles per patient) were administered. The actual dose intensity values were cisplatin 19.6 mg/m2/week and irinotecan 38.2 mg/m2/week. Among the 19 patients, the objective response rate was 95% (19 patients), with 9 patients (47%) having a complete response (CR). The major grade 3/4 hematological toxicities were neutropenia (35% of cycles), anemia (7% of cycles), thrombocytopenia (7% of cycles). Febrile neutropenia was 4% of cycles. The predominant grade 3/4 non-hematological toxicities was diarrhea (5% of cycles). Toxicities was not significantly different with concurrent administration of irinotecan and cisplatin with radiotherapy, except grade 3/4 radiation esophagitis (10% of patients). No treatment-related deaths were observed. The 1-year and 2-year survival rate of eligible patients was 89% (16/18) and 47% (9/18), respectively. CONCLUSION: Three-week schedule of irinotecan plus cisplatin followed by concurrent IP plus hyperfractionated thoracic radiotherapy is an effective treatment for limited disease small-cell lung cancer, with acceptable toxicity.
Subject(s)
Humans , Anemia , Appointments and Schedules , Chemoradiotherapy , Cisplatin , Cranial Irradiation , Diarrhea , DNA Topoisomerases, Type I , Drug Therapy , Esophagitis , Febrile Neutropenia , Follow-Up Studies , Lung Neoplasms , Neutropenia , Radiotherapy , Small Cell Lung Carcinoma , Survival Rate , Thrombocytopenia , Tomography, X-Ray ComputedABSTRACT
PURPOSE : Since the combination of cisplatin plus gemcitabine (CG) had a significant survival advantage for the treatment of patients with chemotherapynaive advanced or metastatic non-small cell lung cancer (NSCLC), CG combination have been evaluated with different schedules. However, the best schedule is still unclear. We designed to compare the efficacy and toxicity of CG combination chemotherapy in two different doses of gemcitabine (1,000 or 1,250 mg/m2 3-weekly). MATERIALS AND METHODS : We randomized patients with stage III or IV NSCLC into either gemcitabine 1,250 mg/m2 or gemcitabine 1,000 mg/m2. Patients received cisplatin 60 mg/m2 intravenously on day1 of each 3-week cycle. Gemcitabine was administered intravenously on days 1 and 8 of each 3-week cycle. RESULTS : From April 2002 until July 2004, 125 patients were enrolled from four university hospitals (55 patients in the gemcitabine 1,000 mg/m2 arm and 70 patients in the gemcitabine 1,250 mg/m2 arm). Response rates were not significantly different in both arms (56.4% vs. 55.7%). However, grade 3 neutropenia was significantly lower in gemcitabine 1,000 mg/m2 arm compared to gemcitabine 1,250 mg/m2 arm (11.0% vs. 15.8%). No differences in non-haematologic toxicities in both arms except anorexia were observed. The median survival was 13.4 months for gemcitabine 1,000 mg group compared with 15.8 months for gemcitabine 1,250 mg group. There were no statistically significant differences in survival between the groups. CONCLUSION : For stage III or IV non-small cell lung cancer, combination chemotherapy with gemcitabine 1,000 mg/m2 showed equivalent response rate with lesser neutropenia and anorexia compared to treatment with gemcitabine 1,250 mg/m2