Drug resistance in clinical practice: patterns of treatment failure in advanced breast and ovarian cancer.

1986 ◽  
Vol 4 (6) ◽  
pp. 952-957 ◽  
Author(s):  
P R Harnett ◽  
F Kirsten ◽  
M H Tattersall
Keyword(s):  
Ovarian Cancer ◽  
Treatment Failure ◽  
Disease Progression ◽  
Progressive Disease ◽  
Complete Response ◽  
Advanced Breast ◽  
New Disease ◽  
Breast Cancer Patients ◽  
Breast And Ovarian Cancer ◽  
Disease Site

We have analyzed the patterns of disease progression in patients with advanced breast and ovarian cancer receiving systemic therapy. Approximately 50% of patients developed progressive disease in a new, rather than a previously documented, disease site. Even when disease progressed in a previously involved disease site, in only half the cases was this identified as the bulk disease site before commencing treatment. The CNS was rarely a new site of disease progression in our patients, a finding that contrasts with a report that identified the CNS as the predominant new disease site in advanced breast cancer patients relapsing following a complete response. Progression of disease on second line treatment commonly occurred at sites of known disease. A number of factors influencing the pattern of disease progression have been examined. Disease progression on endocrine therapy tended to be more common in a previously involved disease site than in patients receiving cytotoxic therapy. There was a trend for patients who progressed within 6 months of chemotherapy to do so in an old site, whereas new disease sites predominated among those progressing later. Strategies for overcoming the causes of treatment failure should take account of the patterns of disease progression. Our results question the wisdom of always ceasing existing therapy when progressive disease is first documented.

scholarly journals The Cost-Effectiveness of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer in Norway

2019 ◽  
Vol 4 (1) ◽  
pp. 238146831882110 ◽  
Author(s):  
Lars Asphaug ◽  
Hans Olav Melberg
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cost Effectiveness ◽  
Gene Panel ◽  
Breast Cancer Patients ◽  
Brca Testing ◽  
Early Onset Breast Cancer ◽  
Breast And Ovarian Cancer ◽  
Quality Adjusted Life ◽  
Multigene Panel

Background. Expansion of routine genetic testing for hereditary breast and ovarian cancer from conventional BRCA testing to a multigene test could improve diagnostic yield and increase the opportunity for cancer prevention in both identified carriers and their relatives. We use an economic decision model to assess whether the current knowledge on non- BRCA mutation prevalence, cancer risk, and patient preferences justifies switching to a multigene panel for testing of early-onset breast cancer patients. Methods. We evaluated routine testing by BRCA testing, a 7-gene panel, and a 14-gene panel using individual-level simulations of annual health state transitions over a lifetime perspective. Breast and ovarian cancer incidence is reduced and posttreatment survival is improved when high-risk mutations are detected and risk-reducing treatment offered. Most model inputs were synthesized from published literature. Intermediate health outcomes included breast and ovarian cancer incidence rates, along with organ-specific cancer mortality. Cost-effectiveness outcomes were health sector costs and quality-adjusted life years. Results. Intermediate health outcomes improved by testing with multigene panels. At a cost-effectiveness threshold of $77,000, a 7-gene panel test with five non- BRCA genes was the optimal strategy with an incremental cost-effectiveness ratio of $53,310 per quality-adjusted life year compared to BRCA-only testing. Limitations. Unable to stratify carriers to specific mutations within genes, we can only make predictions on the gene level, with combined risk estimates for known variants. As mutation prevalence is the absolute upper bound of returns to more expansive testing, the rarity of modelled mutations makes analysis outcomes sensitive to model implementation. Conclusions. A 7-gene panel to diagnose hereditary breast and ovarian cancer in early-onset breast cancer patients can be a cost-effective alternative to current BRCA-only testing in Norway.

Use of liposome encapsulated doxorubicin citrate (LEDC) as a valid drug in patients affected by ovarian cancer suffering from chemotherapy side-effects.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15547-e15547
Author(s):  
Michela Angelucci ◽  
Francesco Plotti ◽  
Ludovico Muzii ◽  
Corrado Terranova ◽  
Carlo De Cicco Nardone ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Side Effects ◽  
Disease Progression ◽  
Wide Spectrum ◽  
Gynecological Cancer ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Cutaneous Toxicity ◽  
Chemotherapy Side Effects ◽  
Palmoplantar Erythrodysesthesia

e15547 Background: Doxorubicin had a wide spectrum of cytotoxic activity in gynecological cancer. Moreover, this drug is associated with chronic cardiac toxicity, often irreversible, which limits lifetime dose. A new liposomal formulations has been developed in the past decades to limite side-effects of doxorubicin: liposome encapsulated doxorubicin citrate (LEDC). In this study we report our experience with LEDC in patients affected by advanced/recurrent gynaecological cancer, suffering from chemotherapy side effects. Methods: From 2000 to December 2008, 43 patients who showed palmoplantar erythrodysesthesia (PPE) during adjuvant or palliative setting treatment of metastatic/recurrent epithelial ovarian cancer. All patients enrolled in the study were treated with liposomal encapsulated doxorubicin citrate (LEDC), administered at the dose of 50 mg/mq every 3 weeks until disease progression or adverse effects. Results: We have enrolled 43 patients who suspended previously chemotherapy treatment for severe PPE. A total of 32 patients completed planned 6 cycles of chemotherapy. After 6 cycles of chemotherapy 3 out of 43 patients (6%) continued to show a complete response, 9 patients (20%) maintained partial response, 16 patients (37%) showed stable disease and 4 patients (9%) suffered disease progression. No severe G3–G4 hematologic toxicity was showed, but neutropenia and anemia continued to be the most common side effects. No cutaneous toxicity were reported. Conclusions: LEDC is a well tolerated drug and a valid alternative in patients affected by ovarian cancer suffering from cutaneous toxicity by other drugs.

Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in advanced ovarian cancer patients not candidates for optimal primary surgery: Safety and effectivenes.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5540-5540
Author(s):  
Vanessa Costa Miranda ◽  
Angelo Bezerra de Sousa Fede ◽  
Carlos Henrique Dos Anjos ◽  
Juliana Ribeiro da Silva ◽  
Fernando Barbosa Sanchez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Disease Progression ◽  
Advanced Ovarian Cancer ◽  
Length Of Hospital Stay ◽  
Complete Response ◽  
Debulking Surgery ◽  
Stage Iiic ◽  
Primary Debulking Surgery

5540 Background: Primary debulking surgery (PDS) has been considered the standard of treatment in advanced ovarian cancer, while neoadjuvant chemotherapy, three cycles followed by interval debulking (ID) surgery, is a valid treatment alternative for patients with non-resectable disease. This study aimed to show the efficacy and safety of six cycles of neoadjuvant chemotherapy (N-CT) followed by cytoreduction, a single institution experience. Methods: Aretrospective analysis was performed of all patients (pts) with advanced ovarian cancer treated with platinum based N-CT, between January/2004 and February/2012. Results: 97 pts underwent N-CT in our institution; 78.1% and 18.8% the patients had extensive stage IIIC or IV disease at diagnosis, respectively. Median age 60 years (36 – 82). Histologic types: serous 84.5%, adenocarcinoma not specified 11.3%, endometrioide 1.0%. A median of six cycles of chemotherapy were performed. Patients did not received chemotherapy after debulking surgery. During the treatment 31.4% had grade 3/4 toxicity, the most commonly observed toxicities were hematologic toxicities and nausea, four (4.1%) patients died during chemotherapy due to disease progression. After N-CT 24.7% achieved clinical complete response, 57.7% partial response and 12.4% disease progression. From this cohort 63.1% underwent a complete resection of all macroscopic and microscopic disease (R0). Median length of hospital stay and postoperative ICU stay was 5 and 0.8 days respectively, surgical complications were not common however five (7.1%) patients needed second surgery due to operatory complications and 19 pts (27.1%) needed blood transfusion after debulking. With a median follow up of 21.8 months (0.5-139.7), median overall survival and chemotherapy-free interval were 57,7 and 9,5 months, respectively. Conclusions: Six cycles of neoadjuvant carboplatin and paclitaxel is safe, effective and does not increase perioperative and postoperative complications for patients with stage IIIC-IV not candidates for optimal/R0 PDS. The overall survival of this cohort is higher than those treated with interval debulking surgery.

Vismodegib, a Hedgehog pathway inhibitor (HPI), in advanced basal cell carcinoma (aBCC): STEVIE study interim analysis in 300 patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9036-9036 ◽  
Author(s):  
Jean Jacques Grob ◽  
Rainer Kunstfeld ◽  
Brigitte Dreno ◽  
Thomas Jouary ◽  
Laurent Mortier ◽  
...  
Keyword(s):  
Disease Progression ◽  
Interim Analysis ◽  
Progressive Disease ◽  
Locally Advanced ◽  
Study Drug ◽  
Complete Response ◽  
Analysis Data ◽  
Primary Objective ◽  
High Rate ◽  
Tumor Control

9036 Background: Therapy options are limited for locally advanced (la) and metastatic (m) BCC. Aberrant Hedgehog (Hh) signaling is the key driver in BCC pathogenesis. Vismodegib, a first-in-class HPI, is approved in the US for use in adults with aBCC. STEVIE is an ongoing study focusing on safety of vismodegib therapy in patients with aBCC. We present data from the third interim analysis (data cutoff: 19 October 2012), which also permits a preliminary assessment of efficacy of vismodegib in the largest study ever conducted in patients with aBCC. Methods: Adult patients with laBCC or mBCC received oral vismodegib 150 mg QD until progressive disease, unacceptable toxicity, or withdrawal. Safety is the primary objective of STEVIE (Common Terminology Criteria for Adverse Events 4.0). Secondary endpoints include efficacy variables. Recruitment is ongoing. Results: This analysis included 300 patients with locally advanced (n=278) or metastatic (n=22) BCC from 11 countries with potential for ≥3-month follow-up. Median treatment duration, including vismodegib interruption, was 176.5 days (range 1-455 days). Common treatment-emergent AEs (TEAEs), typically ≤ grade 2, included muscle spasm (59.3%), alopecia (49.3%), and dysgeusia (41.0%) and were comparable to prior analysis. Serious TEAEs occurred in 53 patients (17.7%). 131 (43.7%) discontinued from the study, mainly due to patient or investigator request (n=41), AEs (n=35), disease progression (n=18) or death (n=13; 7 due to AEs assessed by the investigator as unrelated to study drug, 3 due to AEs not possible to be assessed, 3 due to disease progression). Preliminary best overall response in patients with available tumor assessments (n=251) included complete response (17.5%), partial response (39.8%), stable disease (39.0%) and progressive disease (2.8%). Patient recruitment and monitoring is ongoing. Conclusions: This third interim analysis of STEVIE confirms the previously observed vismodegib safety profile but can also provide further information about the high rate of tumor control with vismodegib in a large series of patients with aBCC. Clinical trial information: 2011-000195-34.

Changes in the fucose content of haptoglobin in breast and ovarian cancer: Association with disease progression

1994 ◽  
Vol 1 (1) ◽  
pp. 37-43 ◽  
Author(s):  
E. Dargan ◽  
S. Thompson ◽  
B. M. J. Cantwell ◽  
R. G. Wilson ◽  
G. A. Turner
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Breast And Ovarian Cancer ◽  
Fucose Content

scholarly journals Analysis of clinical characteristics in breast cancer patients with the Japanese founder mutation of BRCA1 L63X.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 22-22
Author(s):  
Reiko Yoshida ◽  
Mayuko Inuzuka ◽  
Tomoko Watanabe ◽  
Junko Yotsumoto ◽  
Takashi Kuwayama ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Patients ◽  
Clinical Characteristics ◽  
Founder Mutation ◽  
Breast Cancers ◽  
Pathological Features ◽  
Breast Cancer Patients ◽  
Breast And Ovarian Cancer ◽  
Brca1 Mutations

22 Background: Hereditary breast and ovarian cancer (HBOC) is a high-penetrance inherited disease, and founder mutation has been reported in the West. However, there are yet no reports of founder mutation of HBOC on breast cancer in the Japanese population. In this study, we report the breast cancer clinical characteristics of L63X, which is one of the founder mutations in BRCA1 in the Japanese population. Methods: Data on 223 affected breast cancer patients (28 BRCA1 carriers, 19 BRCA2 carriers, and 176 non-carriers) were collected at Showa University in Tokyo from September 2010 to June 2015. In 22 independent mutations of BRCA1, the L63X mutation was detected in 9 patients. Data regarding the age of breast cancer onset, pathological features, clinical features, and family history were collected. Results: The age of onset was no significant differences between the L63X mutation and other BRCA1 mutations (39.7 vs. 38.5years). The proportion of triple negative breast cancer patients was 87.5% in the L63X mutation carriers and 89.5% in other BRCA1 mutation carriers. No patients of the L63X affected bilateral breast cancers. On the other hand, 36.7% of other BRCA1mutations affected bilateral breast cancers. There was no significant difference in pathological features (intrinsic subtype, nuclear grade and ki-67 index). The L63X carriers tended to have a family history of breast cancers. All L63X mutations were detected in the Eastern part of Japan. Conclusions: The breast cancer clinical characteristics of L63X might be considered no different from other types of BRCA1 mutations. Recently, it has been reported that breast and ovarian cancer risks varied according to the type and location of BRCA1/2 mutations. L63X mutation is located in the breast cancer cluster region in BRCA1. Further investigation is necessary for appropriate validation and accumulation of data.

Phase II Study of Vinorelbine With Protracted Fluorouracil Infusion as a Second- or Third-Line Approach for Advanced Breast Cancer Patients Previously Treated With Anthracyclines

2000 ◽  
Vol 18 (19) ◽  
pp. 3370-3377 ◽  
Author(s):  
Alfredo Berruti ◽  
Paola Sperone ◽  
Alberto Bottini ◽  
Gabriella Gorzegno ◽  
Vito Lorusso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Failure ◽  
Advanced Breast Cancer ◽  
Cancer Patients ◽  
Dose Intensity ◽  
Advanced Breast ◽  
Breast Cancer Patients ◽  
Previously Treated ◽  
Experienced Grade ◽  
Experienced Treatment

PURPOSE: To evaluate the feasibility and activity of vinorelbine in association with protracted infusional fluorouracil in patients with advanced breast cancer who were previously treated with anthracycline-containing regimens. PATIENTS AND METHODS: Eighty-three consecutive patients were entered onto the study. Forty-three patients experienced treatment failure or relapse after anthracycline-based, first-line chemotherapy for advanced disease and 29 experienced treatment failure or relapse after first- and second-line approaches; 11 patients experienced progressive disease within 6 months of completion of adjuvant anthracycline therapy. Sites of involvement were as follows: liver involvement, 42 patients (50.6%); lung 24 (28.9%); bone, 49 (59.0%); and skin/lymph nodes, 21 (25.3%). Treatment consisted of vinorelbine 30 mg/m2 administered on days 1 and 15 every 28 days and fluorouracil 200 mg/m2/d given continuously over a 24-hour period. RESULTS: Toxicity was recorded for 441 cycles. The scheme was well tolerated: grade 1/2 nausea/vomiting occurred in 13 patients (15.6%), grade 1/2 diarrhea in nine (10.8%), and grade 2/3 stomatitis in six (7.2%). Three patients (3.6%) experienced grade 3/4 leukopenia and four (4.8%) experienced grade 2/3 anemia. Grade 2/3 neurologic toxicity was observed in three cases (3.6%), and grade 2/3 hand-foot syndrome was observed in three (3.6%). The median relative dose-intensity was 92% and 100% for vinorelbine and fluorouracil, respectively. Six patients (7.2%) attained a complete clinical response and 45 (54.2%) attained a partial response, for an overall response rate of 61.4% (95% confidence interval, 50.9% to 71.9%). Twenty-one patients (25.3%) obtained disease stabilization, and 11 (13.3%) experienced disease progression. Median time to progression in responding patients was 15 months; median overall survival of the entire population was 22 months. CONCLUSION: Vinorelbine associated with protracted infusional fluorouracil is an active and manageable scheme in advanced breast cancer patients previously treated with anthracyclines. The response obtained is durable.

Weekly topotecan and biweekly bevacizumab in recurrent and progressive ovarian carcinoma: A single institution experience for third-line or greater treatment.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16553-e16553
Author(s):  
Kassondra S Grzankowski ◽  
Shashikant B. Lele ◽  
John Pietkiewicz
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Toxicity Profile ◽  
Single Institution ◽  
Free Survival ◽  
Early Use ◽  
Third Line

e16553 Background: The toxicity and efficacy of combined weekly topotecan and weekly bevacizumab in women with recurrent and progressive ovarian cancer. Methods: Reviewed data-base from 1/2003-present (1/2013) identified 15 patients who were treated with topotecan 4mg/m2 on days 1, 8, and 15 and bevacizumab 10mg/kg on days 1 and 15 of a 28-day cycle until progressive disease or excessive toxicity warranted discontinuation. The primary endpoint was progression-free survival. Results: Patients (n = 15) received a median of 4 treatment cycles. Mean number of previous chemotherapy regimens was 5 (range 2-9). Toxicity was generally mild, with neutropenia (20%), gastrointestinal toxicity (20%), pain (26%), anemia requiring transfusion (6%) being the most common adverse events. Two patients required dose adjustment secondary to neutropenia. Patients treated with 5 or more prior regimens had more adverse events, 66% vs. 33%, respectively. No febrile neutropenia or treatment-related deaths occurred. Median PFS and OS were 5.6 months and 5.9 months with 6 (40%) patients progression-free for ≥5 months. Two (13%) patients had complete response, 9 (60%) had stable disease or partial response and were still receiving the above mentioned treatment, and 4 (27%) had progressive disease. Conclusions: Treatment of recurrent and progressive ovarian cancer with weekly Topotecan and biweekly Bevacizumab demonstrates a viable efficacy with acceptable toxicity profile in women with previous multiple lines of treatment; as this becomes a more widely used regimen further investigation will be needed to determine early use of this well tolerated chemotherapy.

Patterns of disease progression to checkpoint inhibitor immunotherapy in patients with stage IV non-small cell lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21674-e21674
Author(s):  
Naomi Fei ◽  
Christina Attia ◽  
Mohammed Almubarak ◽  
Patrick C. Ma ◽  
Malcolm David Mattes
Keyword(s):  
Disease Progression ◽  
Primary Tumor ◽  
Checkpoint Inhibitor ◽  
Stage Iv ◽  
Small Cell ◽  
Tumor Characteristics ◽  
New Disease ◽  
Small Cell Lung ◽  
Disease Site ◽  
Metastatic Sites

e21674 Background: The purpose of this study was to assess patterns of disease progression for patients with metastatic non-small cell lung cancer (NSCLC) on checkpoint inhibitor immunotherapy in order to help guide effective use of targeted radiation therapy to sites of gross disease most likely to progress. Methods: This single center, retrospective study included all patients diagnosed with Stage IV NSCLC between June 2015 and February 2019 who received at least 2 cycles of nivolumab, pembrolizumab, or atezolizumab, with or without concurrent chemotherapy. Immune RECIST criteria were used to assess patterns of disease progression, and progression-free survival (PFS), excluding irradiated tumors. Descriptive statistics were used to report baseline patient and tumor characteristics. The Chi square and log-rank tests were used to determine whether any baseline clinical characteristics were associated with progressive disease in initial sites only (vs. new or combined sites), and PFS, respectively. Factors assessed included initial metastatic sites, tumor histology, performance status, PD-L1 expression, untreated primary tumor, history of brain metastasis, number of metastatic sites involved, and use of concurrent chemo-immunotherapy. Results: Among 143 eligible patients with a median follow-up of 11 months, 97 (68%) developed disease progression. Of these, 67 patients (69.1%) progressed only at initial disease site(s), 10 patients (10.3%) progressed only at new disease site(s), and 20 patients (20.6%) progressed in both initial and new sites. Rates of disease progression based on tumor location were higher for liver (64%) and lung metastases (61%) than for other metastatic sites (33-36%) or the primary tumor (24%). Only higher PD-L1 expression ( p= 0.002) and absence of lung metastasis ( p= 0.048) at baseline were associated with improved PFS. No baseline characteristics significantly impacted the probability of initial disease site-only progression, though a trend was observed for untreated primary tumor (72% vs. 56%, p= 0.169). Conclusions: The dominant pattern of disease progression for patients with metastatic NSCLC on checkpoint inhibitor immunotherapy is in the initial sites of disease alone, whereas only 10% of patients progressed in new disease site(s) alone, suggesting a potential role for local radiation therapy as a complementary treatment modality. Pre-treatment patient and tumor characteristics did not predict patients most likely to benefit.

512 Taxol (tax) and escalating doses of ifosfamide (IFO) in advanced breast and ovarian cancer patients (PTS)

1995 ◽  
Vol 31 ◽  
pp. S109
Author(s):  
A. Romanini ◽  
P.G. Giannessi ◽  
M. Conti ◽  
M. Da Prato ◽  
A. Tognoni ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Advanced Breast ◽  
Breast And Ovarian Cancer
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