Complete response with pegylated liposomal doxorubicin as a second-line therapy in metastatic ovarian carcinosarcoma: Significance of assessment of the response by FDG-PET

PURPOSE: To evaluate the dose, toxicity, and efficacy of paclitaxel in combination with ifosfamide and cisplatin as salvage therapy for patients with relapsed testicular germ cell tumors (GCTs). PATIENTS AND METHODS: Thirty patients with previously treated GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. All had favorable prognostic features for response (testis primary tumor site and prior complete response to first-line chemotherapy program). Four cycles of paclitaxel, ifosfamide 5 g/m2, and cisplatin 100 mg/m2 were given 21 days apart with granulocyte colony-stimulating factor support, followed by resection of radiographic residua. The dose of paclitaxel was increased among cohorts with dose levels of 175, 215, and 250 mg/m2; the largest dose was selected for the phase II part of the trial. RESULTS: Twenty-three (77%) of 30 patients achieved a complete response to chemotherapy alone, and one patient achieved a durable partial response with normal tumor markers. Therefore, 24 (80%) achieved a favorable response. Eleven patients with normalized markers after chemotherapy underwent resection of residual tissue, with only necrosis found in 10 and mature teratoma in one. Two patients relapsed, and 22 (73%) of the favorable responses remain durable at a median follow-up duration of 33 months. Myelosuppression was the major toxicity, and two patients had grade 3 neurotoxicity. CONCLUSION: Four cycles of TIP was associated with a high proportion of patients who achieved a complete response, a lack of relapse, and relative tolerability as an ifosfamide-containing salvage regimen for testicular GCTs. The high durable complete response proportion emphasizes the importance of patient selection according to prognostic factors for a favorable outcome to conventional-dose salvage therapy.

Download Full-text

Comparative analysis of the effectiveness of second-line bevacizumab plus chemotherapy in second-line therapy in metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.619 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 619-619 ◽

Cited By ~ 1

Author(s):

Kaldigul Smagulova

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Progression Free Survival ◽

Complete Response ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy ◽

Group 2 ◽

Group 1

619 Background: Advances in molecular biology and a wide introduction to the practice of targeted therapies have improved outcomes and significantly affect the overall survival of patients. To investigate the efficacy and safety of bevacizumab (BEV) beyond first progression combined with chemotherapy (CT) in patients with metastatic colorectal cancer. Methods: 68 patients with mCRC who received chemotherapy treatment at the Department of the Kazakh Research Institute of Oncology and Radiology. Selecting second-line chemotherapy based on oxaliplatin or irinotecan depended of an earlier first-line therapy (FOLFOX, FOLFIRI). The survival rate was calculated by Kaplan-Meier, comparison of survival curves was performed by log-rank. Results: The study included 68 patients, who were randomized from February 2009 to November 2011(to 33 [48.5%] BEV + CT and 35 [51.5%] to CT alone). Analysis of the immediate results of treatment showed that in neither case was not achieved complete response of the tumor. Partial regression in group 1 – 11 (33.3 ± 8.2)%, and group 2 - in 9 (25.7 ± 7.3)%. Stabilization is achieved in 20 (60.6 ± 8.5)% and 23 (6.7 ± 8.0)% of cases, respectively. The progression of the disease was observed in the group 1 in 2 (6.1 ± 4.1)% and 3 (8.6 ± 4.7)% of cases. Median progression-free survival (PFS) and overall survival (OS) was 11.5 months (7-16) and 12.2 months in group 1, and 9.7 months (6-13.2) (PFS), 9.1 months(OS) in group 2, respectively. The adverse event profile was consistent with previously reported data for BEV + CT. BEV-related significant adverse events included bleeding grade 3-4 (1.5 %) and venous thrombosis (2.3 %). Conclusions: Our findings demonstrate that BEV + CT continued beyond progression significantly prolong OS and PFS in second-line therapy mCRC.

Download Full-text

Results of the Russian Registry of Primary Immune Thrombocytopenia in Pediatric Patients

Blood ◽

10.1182/blood.v126.23.4643.4643 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4643-4643

Author(s):

Anastasia Shamardina ◽

Inna Markova ◽

Tatyana Sycheva ◽

Elena Volodicheva ◽

Alexander Rumyantsev ◽

...

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenia ◽

Disease Onset ◽

Specific Treatment ◽

Complete Response ◽

Second Line ◽

Second Line Therapy ◽

Chronic Itp ◽

Line Therapy ◽

Clinically Significant

Abstract Study objectives We aim to evaluate disease characteristics and treatment practices of pediatric pts. with Immune thrombocytopenia (ITP) in Russia. Materials and methods The ITP Registry was a multicenter, prospective, observational cohort study. Inclusion criteria: diagnosis of primary ITP, informed consent of the patient/guardians. Exclusion criteria: secondary or congenital thrombocytopenia. Data from medical records were registered in the e-CRF in average every 3 months. Descriptive statistics were used. Patients were registered since June 2011 till June 2014. Results Ninety-three pediatric pts, 46 male (49.5%) and 47 female (50.5%) with a median age 8.4 yrs (range 0.5-17.8) from 5 centers in various regions of Russia were included. The mean observation period reached 17.1 ± 6.5 mo (range1.4 to 28.6 months). Seventy (75.3%) pts had acute and 24.7% pts had insidious disease onset. The presence of trigger factors for ITP development was found in more than half of the cases (in 61.3% of patients), they are listed in Table 1. Table 1. Triggers N % No triggers 36 38.7% Infection 46 49.5% Vaccination 8 8.6% Other 3 3.2% Total 93 100% Median disease duration at enrollment was 1.07 years (range 0 to 16.7 yrs). ITP duration shorter than 5 years at the enrollment was reported in 89.2% pts, up to 1 year - in 43 (46.2%), 1- 5 years - in 40 (43%), 5-10 years - in 8 (8.6%), >10 years - in 2 (2.2%) pts. Newly diagnosed ITP was reported in 35 (37.6 %) pts, persistent ITP - in 12 (12.9 %), chronic ITP - in 46 (49.5 %) pts.Median platelets count was 12,0 x 109/L (range 0.0 - 72.0 109/L). Ninety-two (98%) pts experienced hemorrhagic manifestations during the course of ITP: skin hemorrhages - in 98.9%, oral bleeding - in 15.1%, epistaxis - in 36.6%, gastrointestinal bleeding - in 1.1%, intracranial bleeding - in 1.1%, hematuria - in 1.1%, and other hemorrhages - in 9.7% of pts. Relationship between hemorrhagic syndrome and platelet count at the enrollment is provided in table 2. Table 2. Relationship between hemorrhagic syndrome and platelet count (at enrollment) Hemorrhage highest grade according to WHO Platelet count (visit 1) Total pts / % < 30,000 30,000 -50,000 >50,000 0 3 5.5% 3 5.5% 49 89.1% 55 100% 1 11 40.7% 5 18.5% 11 40.7% 27 100% 2 5 62.5% 0 0% 3 37.5% 8 100% 3 2 66.7% 1 33.3% 0 0% 3 100% Total 21 22,6% 9 9.7% 63 67.7% 93 100% Severe course of ITP after enrollment was observed in 12 (13%) pts (of whose 6 (6.5%) had clinically significant hemorrhage at the disease onset and 6 (6.5%) had new clinically significant hemorrhages during follow-up period. Refractory ITP at enrollment was reported in 9 (9.7%) pts and was associated with the resistance to the first-, second- and subsequent lines of therapy. At enrollment 42 (45.2%) pts received specific treatment for ITP. Before enrollment, splenectomy was reported in only 1 (1.1%) 14-years old patient who had a complete response. During the study, splenectomy was performed in 6 (6.6%) pts with chronic ITP; the duration of the disease at the time of splenectomy varied from 2 to 10 years, with average duration of 4.69 years (median - 4.5 years). Complete response to splenectomy was observed in 3 (50%) pts, a partial response - in 2 (33.3%), no response - in 1 (16.7%) patient. Loss of response to splenectomy was not reported. During the study, severe ITP was reported in 8 (8.7%) pts, 41 (44.6%) pt had various hemorrhagic manifestations of ITP at least at 1 visit, grade IV hemorrhagic syndrome was not reported. Thirty-eight (41%) pts received 1-st line treatment: glucocorticosteroids (GCS) - 23 (60.5%) pts, IVIG - 5 (13.2%), alfa-interferons -16 pts (42.1%). Twenty-three pts (24.7%) received second-line therapy: GCS - 1 (4.3%), IVIG -1 (4.3%), immunosupression - 1 (4.3%), rituximab - 2 (8.7%), romiplostim - 11 (47.8%), eltrombopag - 14 (60.9%). Conclusion For the first time new information on the features of the disease and patterns of management of pediatric pts with primary ITP in Russia was obtained in a prospective study. Interestingly, the preferred therapy for the 2nd or subsequent lines are TPO receptor agonists used outside the approved indications in research institutions, based on published clinical trial data. Splenectomy rate before and during the study was only 7.5% (7 pts) with chronic ITP; in 1 child (14.3%) splenectomy was ineffective. Low acceptance of splenectomy suggests TPO-mimetics as potential second-line therapy. In total, good disease control is achievable in the majority of pediatric pts with ITP. Disclosures Off Label Use: use of TPO-mimetics in children.

Download Full-text

Efficacy of Second Line Agents Dapsone & Azathioprine in Children & Adults with Immune Thrombocytopenia: Single Centre Experience from India

Blood ◽

10.1182/blood.v126.23.1064.1064 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1064-1064

Author(s):

Venkatesh Shreeganesh Ekbote ◽

Biju George ◽

Vikram Mathews ◽

Kavitha Lakshmi ◽

Abhijeet Ganapule ◽

...

Keyword(s):

Response Rate ◽

Complete Response ◽

Second Line ◽

Second Line Therapy ◽

Total N ◽

Overall Response ◽

Line Therapy ◽

Number Of Patients ◽

Increased Risk ◽

Azathioprine Group

Abstract There are approximately 10 therapeutic agents listed as second line therapy for steroid refractory or relapsed ITP but there are no clear guidelines for timing & order of their use or that of splenectomy. At our center, we have used dapsone or azathioprine as second line therapy prior to splenectomy in such patients who do not have critical bleeding. This study describes the outcome of that approach. Three hundred patients fulfilling ITP International Working Group definition of steroid non-response & relapse ITP (Rodeghiero et al Blood 2009) were included. Response to treatment was assessed using American Society of Hematology 2011 guidelines (Neunert et al Blood 2011). This analysis was approved by the institutional ethics committee. Patients received either dapsone (n = 170) at 1-2 mg/kg/day or azathioprine (n = 130) at 1-3 mg/kg/day in escalating doses based on physician preferences. Additional intermittent corticosteroids were given in 36 patients. Data was retrieved from individual medical records and electronic database. Statistical analysis was performed using SPSS version 16.0 Results: Baseline characteristics of the patients & outcome are described in Table 1. After 3 months of therapy, overall response was 58.6% while it was 58.8% for the dapsone group and 58.5% for azathioprine group. The number of patients achieving complete & partial response was 46% & 12.7% for overall group, 45.9% & 13% for dapsone group & 46.2% & 12.3% for azathioprine group. The median duration of response was 35 months (2-74 months) and was significantly longer with azathioprine - 60 months (2-60 months) compared to 27 months (5-74 months) with dapsone (p=0.015). Therapy was well tolerated with 4 patients discontinuing dapsone (methemoglobinemia, dapsone syndrome) and 2 discontinuing azathioprine (cytopenia). There were no deaths. At a median follow up of 33 months (24-42 months), 67 (38%) of the 176 responders have relapsed. These included 49 patients that relapsed while on therapy and 18 that relapsed after cessation of therapy. Relapses were significantly more common with dapsone (40.3%) than azathioprine (20.4%) (p=0.002). The median time to relapse while on therapy was 14 months for both agents. Any response to second line therapy less than complete response (p=0.030) & steroid nonresponsive ITP (p=0.042) were significantly associated with increased risk of relapse on therapy. Overall, 59.6% patients responding to dapsone and & 79.5% of patients responding to azathioprine continue to remain in remission both on & off therapy. Patients who switched to dapsone at the time of relapse showed significantly better response rate - 54% than azathioprine - 22.2% (p<0.001). Forty one patients who failed second line therapy eventually underwent splenectomy, with a response rate of 70.7%. In conclusion, the use of dapsone & azathioprine appears to be a safe approach, with need for splenectomy only in a few patients. The optimal dose & duration of therapy for these agents needs further evaluation in prospective studies. Table 1. Patient Characteristics Characteristics Total (%) N = 300 Dapsone (%) n = 170 Azathioprine (%) n = 130 P value Children 104 (34.7) 64(37.7) 40(30.7) ns Adults 196 (65.3) 106(62.3) 90(69.3) ns Male:Female Ratio 0.56:1 0.68:1 0.42:1 0.069 Median ITP Duration (months) 5 (1-262) 4 (1-262) 6 (1-146) ns Steroid Non-responsive 144 90 (52.9) 54 (41.5) 0.062 Relapsed ITP 156 80 (47.1) 76 (58.5) 0.062 Overall Response 176 (58.6) 100 (58.8) 76 (58.5) ns Complete Response 138 (46) 78 (45.9) 60 (46.2) ns Relapse rates 67/176 (38) 40.3% 20.4% 0.002 ns = not significant Disclosures No relevant conflicts of interest to declare.

Download Full-text

Association between antibiotic exposure and survival in patients with hepatocellular carcinoma treated with nivolumab.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16186 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16186-e16186

Author(s):

Kanan Alshammari ◽

Futoon Alsugheir ◽

Mohammad Aldawoud ◽

Ashwaq Alolayan ◽

Mohammad Ahmad Algarni ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Survival Data ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Complete Response ◽

Rank Test ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy ◽

Number Of Patients

e16186 Background: Nivolumab, an immune checkpoint inhibitor, has improved the outcomes of patients with hepatocellular carcinoma (HCC). It is approved for HCC patients previously treated with sorafenib. Outcomes have been reported in previous studies, in malignancies other than HCC, to be worse when patients have been exposed to antibiotics while receiving immune checkpoint inhibitors. We aimed to evaluate the effects of antibiotics on survival in HCC patients treated with nivolumab. Methods: We performed a retrospective review of 59 patients with advanced HCC that have been treated with nivolumab in two academic centers in Saudi Arabia. Patient characteristics, tumor data, antibiotic use (2 weeks prior, during, and 4 weeks after nivolumab therapy), survival data, and other factors were collected. Log-rank test analysis was performed to test the difference in overall survival (OS) time with and without antibiotics use. Results: The majority of patients were males (n=51, 85%), and 38 were Child-Pugh A (64%). A large number of patients had Barcelona Clinic Liver Cancer (BCLC) stage C tumors (n=42, 71%), and 20 patients (34%) used antibiotics. Most patients received nivolumab as second-line therapy after exposure to sorafenib (n=49, 83%). In patients who received nivolumab as first- or second-line therapy (n=57) and did not receive antibiotics, the median OS was double that of patients who received antibiotics (10 vs. 4.5 months, P=0.04). In child A patients who received nivolumab as second-line therapy (n=32), those who were exposed to antibiotics had a statistically significant shorter median OS compared to those who did not (5.5 vs. 20 months, P=0.04). More patients achieved partial response, or complete response (as per modified RECIST criteria) in the cohort that did not receive antibiotics compared to patients who received antibiotics (21% vs. 15%) but that was not statistically significant (P=0.6). Conclusions: This study shows that HCC patients receiving nivolumab have worse survival if they received antibiotics. Antibiotic mediated alteration of the gut microbiome may impact nivolumab response and shorten patient survival. Although this finding may warrant a prospective larger study but it is consistent with other previous studies. Antibiotics should be used very cautiously when treatment with checkpoint inhibitors is considered.

Download Full-text

Metabolic complete response with vinflunine as second-line therapy in a kidney-transplanted patient with advanced urothelial carcinoma: a case report

BMC Cancer ◽

10.1186/s12885-016-2666-6 ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 3

Author(s):

Paola Bordi ◽

Marcello Tiseo ◽

Giorgio Baldari ◽

Sebastiano Buti

Keyword(s):

Case Report ◽

Urothelial Carcinoma ◽

Complete Response ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy ◽

Advanced Urothelial Carcinoma

Download Full-text

Combination Antibiotic Treatment of Chemotherapy-Induced Neutropenia in Non-Leukemic Patients

Tumori Journal ◽

10.1177/030089168907500508 ◽

1989 ◽

Vol 75 (5) ◽

pp. 443-448

Author(s):

Giampietro Gasparini ◽

Salvatore Turnolo ◽

Giuseppe Toffoli ◽

Renato Talamini ◽

Alberto Vaglia ◽

...

Keyword(s):

Median Duration ◽

Bacterial Infections ◽

Performance Status ◽

Unknown Origin ◽

Complete Response ◽

Second Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Neutropenic Patients

The use of more aggressive chemotherapies in the treatment of patients with some tumors has caused a higher frequency of neutropenia and subsequent serious infections. To verify the role in these patients of a combination therapy of amikacin (300 mg/m2 i.v. every 12 hours) plus ceftazidime (2 g/m2 i.v. every 8 hours) adminsitered as initial empiric treatment, followed in non-responsive cases by a second-line therapy with clindamycin (300 mg/m2 i.v. every 8 hours), we conducted a prospective study in 45 febrile episodes (temperature ≥38.5 °C) in neutropenic patients (neutrophils ≤500/ml). The patients' median age was 58 (range, 19-80); 29 were women and 16 were men. The median performance status was 50 (range, 30-90), and 71 % of the patients had progressive tumoral disease. Before antibiotic therapy the median duration of fever was 12 hours (range, 4-48 hours). The median granulocyte count was 350/ml (range, 100-500 cells/ml), and the median peak temperature was 38.8 °C (range, 38.5-41 °C). The median time for neutrophils to rise towards 1000/ml was 4 days (range, 2-12), and the median duration of therapy was 8 days (range, 3-12). Documented bacterial infections were present in 28 patients whereas 17 had clinically possible infections or fever of unknown origin. The infection sites in microbiologically documented infections were: septicemia (12), multiple sites (4), tonsillitis (4), urinary tract (4), pneumonia (2) and fistula (2). Complete response to first-line therapy was obtained in 36 out of 45 episodes (80 %; 95 % confidence limits from 65 % to 90 %). Five out of 8 cases responded to second-line therapy with clindamycin for an overall recovery rate of 91 %. The amikacin-ceftazidime combination followed by clindamycin in non-responsive cases is effective, with moderate toxicity in non-leukemic febrile neutropenic patients.

Download Full-text