Second-line randomized trials in epithelial ovarian cancer

2008 ◽  
Vol 18 (Suppl 1) ◽  
pp. 59-66 ◽  
Author(s):  
J. B. Vermorken
Keyword(s):  
Ovarian Cancer ◽  
Randomized Trials ◽  
Single Agent ◽  
Complete Response ◽  
Recurrent Ovarian Cancer ◽  
First Line ◽  
Symptomatic Disease ◽  
First Line Therapy ◽  
Line Therapy ◽  
Response To Chemotherapy

Important issues in the treatment of patients with recurrent ovarian cancer (ROC) are 1) to delay the time to symptomatic disease, 2) to reduce symptoms in case of symptomatic disease, 3) to optimize quality of life, and 4) to prolong overall survival. However, response assessment and recording of treatment-induced side effects in general get most attention. The likelihood of response to chemotherapy is directly proportional to the length of time between the end of primary chemotherapy and the date of recurrence. Also, the aggressiveness of the recurrence seems related to the prior biological pace of disease progression. For these reasons different disease categories have been identified, ie, platinum/taxane-refractory disease (progressive during first-line stabilization as best response), persistent disease (partial response to first-line therapy), platinum/taxane-resistant disease (clinical complete response [CCR] or no evidence of disease [NED] to/after first line and relapse <6 months), and platinum/taxane-sensitive disease (CCR or NED to/after first line and relapse >6 months). Randomized trials in these different categories did not show a benefit of maintenance or consolidation therapies after first-line therapy but did show differences in tolerability and efficacy (in platinum/taxane-sensitive disease) of different single agents and indicated that in specific circumstances combination chemotherapy is superior to single-agent chemotherapy. However, in all circumstances other aspects such as toxicity (and earlier experienced toxicity), clinical condition, convenience of administration, costs, and patient preference should be considered in the final selection of treatment

scholarly journals Cancer Stem Cell Assay for the Treatment of Platinum-Resistant Recurrent Ovarian Cancer

2021 ◽  
Vol 7 (3) ◽  
pp. 1-9
Author(s):  
Pier Paolo Claudio ◽  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Recurrent Ovarian Cancer ◽  
Treatment Selection ◽  
Cytotoxicity Assay ◽  
First Line ◽  
Cell Assay ◽  
First Line Therapy ◽  
Line Therapy

This data indicates that the drug cytotoxicity assay aimed at targeting CSCs may be a useful tool for optimizing treatment selection when first-line therapy fails, and when there are multiple clinically-acceptable and -equivalent treatments available.

Pan-cancer evaluation of homologous repair deficiency somatic mutations and response to first-line anti-neoplastic therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10535-10535
Author(s):  
Jessica A Lavery ◽  
Samantha Brown ◽  
Gregory J. Riely ◽  
Philippe L. Bedard ◽  
Ben Ho Park ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
De Novo ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Major Mechanism ◽  
First Line Therapy ◽  
Oncogenic Mutation ◽  
Line Therapy ◽  
Response To Chemotherapy

10535 Background: Homologous recombination is a major mechanism of defective DNA repair, but it remains uncertain whether homologous repair deficient (HRD) tumors have favorable prognosis or are more/less likely to respond to treatment than tumors lacking such mutations. Objective: To determine whether lung (NSCLC) and colorectal (CRC) HRD+ tumors have better survival or response to chemotherapy than HRD- tumors. Methods: Patients with de novo stage IV NSCLC or CRC who had next generation sequencing (NGS) between 2015-2018 from one of four cancer centers were identified. Records were curated using the PRISSMM framework to ascertain treatment, overall survival (OS) and progression free survival based on imaging (PFS-I) and oncologists’ notes (PFS-M). Each NSCLC or CRC tumor was categorized as HRD+ if NGS revealed an oncogenic/likely oncogenic mutation in: ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, PALB2, RAD50, RAD51, RAD51C, RTEL1, or MRE11A based on the OncoKB database. The tumor was categorized as HRD- if no oncogenic mutation in any of these genes was evident and HRD indeterminate (HRD?) if no mutation was identified but the panel did not include all genes. OS, PFS-I and PFS-M from start of first line therapy were reported by HRD status. The percentage with a good response to first line therapy (≥2x the median) and exceptional response (≥3x the median) was estimated for each endpoint. Results: For NSCLC 4% were HRD+, 59% HRD- and 37% HRD?. For CRC there were 5% HRD+, 60% HRD- and 35% HRD?. There were no significant differences for any survival endpoint between patients who were HRD+ vs HRD- in univariable analyses. The proportion of good and exceptional responders to first line systemic chemotherapy also did not vary by HRD status, though patients with HRD+ CRC were potentially more likely to be exceptional responders. Similarly, no differences between HRD+ and HRD- tumors were apparent for the subgroup receiving platinum containing therapy. Conclusions: NSCLC and CRC patients with somatic mutations in HRD oncogenic genes did not differ from patients lacking such a mutation with respect to OS or PFS. CRC patients with HRD+ tumors may be more likely to be exceptional responders, but sample sizes are limited. By May, the analysis will include breast and pancreatic cancer cases.[Table: see text]

High-dose, single-agent irinotecan as first-line therapy in the treatment of metastatic colorectal cancer

2002 ◽  
Vol 50 (5) ◽  
pp. 383-391 ◽  
Author(s):  
Ychou M. ◽  
Raoul J. ◽  
Desseigne F. ◽  
Borel C. ◽  
Caroli-Bosc F. ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Single Agent ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Efficacy and safety of aspacytarabine (BST-236) as a single-agent, first-line therapy for patients with acute myeloid leukemia unfit for standard chemotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7007-7007
Author(s):  
Jessica K. Altman ◽  
Jamie Koprivnikar ◽  
James K. McCloskey ◽  
Vamsi Kota ◽  
Olga Frankfurt ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
De Novo ◽  
Single Agent ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
First Line ◽  
Standard Chemotherapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
De Novo Aml

7007 Background: Aspacytarabine (BST-236) is a prodrug of cytarabine, the backbone of acute myeloid leukemia (AML) standard of care chemotherapy, associated with toxicity which precludes its administration in older patients and patients with comorbidities. Aspacytarabine is inactive in its intact prodrug form until cytarabine is gradually released at pharmacokinetics which decrease the systemic exposure to peak toxic cytarabine levels, resulting in reduced systemic toxicity and relative sparing of normal tissues, enabling therapy with high cytarabine doses to patients otherwise unfit to receive it. Methods: A phase 2b open-label, single-arm study to evaluate the efficacy and safety of aspacytarabine as a first-line single-agent therapy in newly-diagnosed AML patients unfit for standard chemotherapy (NCT03435848). Aspacytarabine is administrated at 4.5 g/m2/d (containing 3 g/m2/d cytarabine) in 1-2 induction and 1-3 consolidation courses, each consisting of 6 daily 1-hour infusions. Patients with secondary AML, prior hypomethylating agent (HMA) therapy, and therapy-related AML, are eligible. Results: To date, in the ongoing study, 46 newly-diagnosed AML patients unfit for standard chemotherapy (median age 75 years) were treated with aspacytarabine and completed 1-4 courses of 4.5 g/m2/d aspacytarabine, including 26 patients (63%) with de novo AML and 17 (37%) with secondary AML. Six patients (13%) were previously treated with HMA (median 12 courses). The baseline median bone marrow blasts was 52%, and 54% and 29% of patients had adverse or intermediate European LeukemiaNet (ELN) score, respectively. Twenty (43%) patients had ECOG 2. Aspacytarabine is safe and well-tolerated in repeated-course administration. Grade > 2 drug-related adverse events include mainly hematological events and infections. The 30-day mortality rate is 11%. Of 43 patients evaluable for efficacy analysis to date, 15 patients (35%) reached a complete remission (CR) following 1 (13 patients) or 2 (2 patients) induction courses, all with complete hematological recovery (median 27.5 days, range 22-39 days). The CR rates in de novo AML patients and patients with adverse ELN score are 46% and 33%, respectively. Of the 11 patients evaluable to date for minimal residual disease (MRD) flow cytometry test, 8 are MRD negative (73%). While aspacytarabine treatment consists of a limited number of courses, median duration of response and median overall survival for responders are not reached at 12 and 24 months, respectively (end of follow up). Updated results will be presented at the meeting. Conclusions: The cumulative clinical data suggest that aspacytarabine, a time-limited single-agent treatment, is safe and efficacious as a first-line therapy for patients who are unfit for intensive chemotherapy, which may establish it as a new tolerable AML chemotherapy backbone. Clinical trial information: NCT03435848.

scholarly journals CEPP(B): an effective and well-tolerated regimen in poor-risk, aggressive non-Hodgkin's lymphoma

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1293-1298 ◽  
Author(s):  
NJ Chao ◽  
SA Rosenberg ◽  
SJ Horning
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Medical Center ◽  
Palliative Therapy ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract Eighty-three patients with intermediate- or high-grade non-Hodgkin's lymphoma were treated with CEPP(B) (cyclophosphamide, etoposide [VP- 16], procarbazine, and prednisone with or without bleomycin) chemotherapy at Stanford University Medical Center (Stanford, CA) from January 1982 through June 1989. Sixty-nine received CEPP(B) as second- line or subsequent therapy after relapse from previous combination chemotherapy, and 14 patients received CEPP(B) as first-line therapy. Of 75 patients evaluable for response, 30 patients (40%) achieved a complete response (CR) and 24 patients (32%) achieved a partial response (PR), providing an overall response rate of 72%. Complete responses were recorded on 21 of 61 (34%) patients with recurrent disease and 9 of the 14 patients who received CEPP(B) as first line therapy (64%). Myelosuppression was the major side effect of treatment, resulting in eight neutropenic-febrile episodes from a total of 253 courses. A single fatal toxic event occurred on a patient who developed adult respiratory distress syndrome. Overall, CEPP(B) was well- tolerated and proved to be effective palliative therapy for patients with non-Hodgkin's lymphoma after relapse. As such, CEPP(B) may be considered for cytoreduction before ablative therapy and bone marrow transplantation. CEPP(B) may also be considered for initial therapy in selected patients who cannot tolerate doxorubicin-containing regimens.

Longitudinal Evaluation of Minimal Residual Disease in Patients with Multiple Myeloma who Achieve Complete Response After First Line Therapy

2019 ◽  
Vol 19 (10) ◽  
pp. e185-e186
Author(s):  
Ioannis V. Kostopoulos ◽  
Efstathios Kastritis ◽  
Aristea-Maria Papanota ◽  
Paraskevi Micheli ◽  
Panagiotis Malandrakis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Complete Response ◽  
First Line ◽  
Longitudinal Evaluation ◽  
First Line Therapy ◽  
Line Therapy ◽  
Minimal Residual
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