Capecitabine therapy in recurrent/metastatic nasopharyngeal cancers.

e18515 Background: A wide range of chemotherapeutic agents have demonstrated antitumor activity in patients with recurrent or metastatic Nasopharyngeal Cancers (NPC). These therapeutic agents have different efficacy and toxicity profile. Capecitabine monotherapy had activity in recurrent/metastatic NPC based on small previous retrospective studies. The primary objective is to evaluate the overall response rate and tolerability of capecitabine in recurrent/metastatic NPC. Methods: A retrospective electronic chart review performed for 51 cases of recurrent/metastatic NPC patients who received capecitabine 1000-1,250 mg/m² twice daily two weeks on, one week off between 2011 to 2019 at King Faisal Specialist Hospital & Research Center (KFSH&RC). The Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 was used. Results: The median age at diagnosis was 42 years. 98% had a non-keratinized undifferentiated squamous cell carcinoma (Grade III). The most common sites for metastases were Bone (58.3%), Lung (50.0%), and liver (45.8%). 95% of patients received platinum-based chemotherapy and radiation therapy as the primary treatment. Capecitabine was used as the second or third line of treatment in the metastatic setting 45.1% and 43.1%, respectively. The patients tolerated the standard dose for a median of 6 cycles; only 20.0% of patients required a 25% dose reduction. The best response for capecitabine was complete response in 8 patients (15.7%), partial response in 14 patients (27.5%), stable disease in 10 patients, (19.6%), with a clinical benefit achieved in 32 patients (62.7%), and progressive disease in 16 patients (31.4%). The overall response rate to capecitabine was 43.2%, which was consistent regardless of the site of metastasis. The median progression-free survival was seven months (95%.CI: 5.3 -8.8). The one and three-year survival rates were 79% and 53%, respectively. Capecitabine was generally tolerated, the most common grade I & II adverse events were hand-foot syndrome (HFS) in 9 patients (20.5%), fatigue in 8 patients (15.7%), Diarrhea in 6 patients (11.7%), anemia in 5 patients (9.8 %), thrombocytopenia in 4 patients (7.8%) and neutropenia in 2 patients (4.0%). The most common grade III & IV was HFS in 3 patients (6%) and fatigue in one patient (2%) that led to treatment discontinuation after the first cycle. Conclusions: Capecitabine in Recurrent/Metastatic NPC is an effective and well-tolerated oral agent; however, a randomized prospective trial to evaluate capecitabine efficacy in this setting still recommended.

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Everolimus and exemestane in hormone receptor-positive advanced breast cancer: A comprehensive cancer center’s experience.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13017 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e13017-e13017

Author(s):

Inês Moreira ◽

Marta Ferreira ◽

Ana Afonso ◽

Ana Ferreira ◽

Ana Rodrigues ◽

...

Keyword(s):

Breast Cancer ◽

Adverse Events ◽

Advanced Breast Cancer ◽

Endocrine Therapy ◽

Hormone Receptor ◽

Overall Response Rate ◽

Response Rate ◽

Advanced Breast ◽

Overall Response ◽

Hormone Receptor Positive

e13017 Background: Activation of the mammalian target of rapamycin intracellular signaling pathway is one of the mechanisms of endocrine resistance in breast cancer. The addition of everolimus to exemestane improves progression-free survival (PFS) in patients with hormone receptor positive (HR+) advanced breast cancer (ABC) previously treated with nonsteroidal aromatase inhibitors (NSAIs). The aim of this study was to assess the effectiveness and safety of everolimus plus exemestane in patients with HR+ ABC. Methods: We retrospectively evaluated patients with HR+, HER2 negative ABC treated with everolimus/exemestane that recurred or progressed during/after treatment with NSAIs in a portuguese comprehensive cancer center. Study endpoints were PFS, overall survival (OS), overall response rate and adverse events. Results: Between April 2014 and September 2020, 63 female patients were treated with everolimus/exemestane. Median age was 59 years (36-79), and all had performance status ECOG ≤2. Seventeen (27.0%) patients had bone metastasis alone, 39 (61.9%) had bone and visceral metastasis, 25 (39.7%) had metastasis in 3 or more sites and 87.3% had previous hormone-sensitive disease. Before everolimus/exemestane, 61 (96.8%) patients were being treated with palliative endocrine therapy (alone or in combination with CDK4/6 inhibitors) or chemotherapy (ChT) and 2 (3.2%) patients were under adjuvant endocrine therapy. Median follow-up time was 12.8 months (1.4-74.6), with 39 patients alive. Overall response rate was 14.3% (1 complete response and 8 partial responses) and 45 patients had stable disease. Median PFS was 5.6 months (CI95% 2.4-8.8) and median OS was 25.4 months (CI95% 10.3-40.5). Subgroup analysis regarding PFS was statistically significant for previous treatment with CDK4/6 inhibitors (p = 0.026) and for site of metastasis (p = 0.025). In the subgroup of patients that previously underwent palliative ChT, median PFS was 4.0 months (CI95% 0.2-9.6) and median OS was 18.6 months (CI95% 8.2-29.0). For patients that did not receive previous palliative ChT, median PFS was 5.8 months (CI95% 3.8-7.8) and median OS was 43.5 months (CI95% 2.0-85.0). Grade 3 and 4 adverse events occurred in 21 (33.3%) patients, and were: nausea, anorexia, rash, headache, haematologic toxicity, hepatic cytolysis, hyperglycaemia, pneumonitis, oral mucositis and acute kidney failure with need for haemodialysis. Fifty-five (87.3%) patients suspended everolimus, 34 (54.0%) due to disease progression and 21 (33.3%) due to toxicity. Conclusions: Our results confirm the effectiveness and safety of everolimus/exemestane in real-world setting and support its use mainly before palliative ChT. Everolimus/exemestane in HR+ ABC is feasible in the clinic, with toxicity manageable under close surveillance.

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Phase II Study of Lenvatinib in Patients With Progressive, Recurrent or Metastatic Adenoid Cystic Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.18.01859 ◽

2019 ◽

Vol 37 (18) ◽

pp. 1529-1537 ◽

Cited By ~ 22

Author(s):

Vatche Tchekmedyian ◽

Eric J. Sherman ◽

Lara Dunn ◽

Crystal Tran ◽

Shrujal Baxi ◽

...

Keyword(s):

Adverse Events ◽

Adenoid Cystic Carcinoma ◽

Phase Ii ◽

Overall Response Rate ◽

Response Rate ◽

Progression Free Survival ◽

Free Survival ◽

Overall Response ◽

End Point ◽

Adenoid Cystic

PURPOSE Recurrent or metastatic adenoid cystic carcinoma (R/M ACC) is a malignant neoplasm of predominantly salivary gland origin for which effective therapies are lacking. We conducted a phase II trial evaluating the multitargeted tyrosine kinase inhibitor lenvatinib in patients with R/M ACC. PATIENTS AND METHODS This study was conducted with a two-stage minimax design. Patients with histologically confirmed R/M ACC of any primary site with radiographic and/or symptomatic progression were eligible. Any prior therapy was allowed except previous lenvatinib. Patients received lenvatinib 24 mg orally per day. The primary end point was overall response rate. Secondary end points were progression-free survival and safety. An exploratory analysis of how MYB expression and genomic alterations relate to outcomes was conducted. RESULTS Thirty-three patients were enrolled; 32 were evaluable for the primary end point. Five patients (15.6%) had a confirmed partial response, 24 patients (75%) had stable disease, two patients (6.3%) discontinued treatment as a result of toxicity before the first scan, and one patient (3.1%) had progression of disease as best response. Median progression-free survival time was 17.5 months (95% CI, 7.2 months to not reached), although only eight progression events were observed. Patients otherwise were removed for toxicity (n = 5), as a result of withdrawal of consent (n = 9), or at the treating physician’s discretion (n = 6). Twenty-three patients required at least one dose modification, and 18 of 32 patients discontinued lenvatinib for drug-related issues. The most common grade 3 or 4 adverse events were hypertension (n = 9; 28.1%) and oral pain (n = 3; 9.4%). Three grade 4 adverse events were observed (myocardial infarction, n = 1; posterior reversible encephalopathy syndrome, n = 1; and intracranial hemorrhage, n = 1). CONCLUSION This trial met the prespecified overall response rate primary end point, demonstrating antitumor activity with lenvatinib in R/M ACC patients. Toxicity was comparable to previous studies, requiring monitoring and management.

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Capecitabine in patients with platinum-pretreated advanced or recurrent cervical carcinoma: a retrospective study

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2018-000085 ◽

2019 ◽

Vol 29 (2) ◽

pp. 272-276 ◽

Cited By ~ 1

Author(s):

Giuseppa Maltese ◽

Stefano Lepori ◽

Ilaria Sabatucci ◽

Elisa Tripodi ◽

Domenica Lorusso

Keyword(s):

Cervical Cancer ◽

Adverse Events ◽

Cervical Carcinoma ◽

Overall Response Rate ◽

Response Rate ◽

Gynecologic Oncology ◽

Recurrent Cervical Cancer ◽

Oral Capecitabine ◽

Overall Response ◽

Dismal Prognosis

BackgroundCervical cancer is a common malignancy among women and, when recurring, presents a dismal prognosis. After platinum failure, second-line treatments report response rates ranging from 3–15%, a median progression-free survival of about 3 months and a median overall survival of about 5.5 months.To retrospectively evaluate the activity and safety of capecitabine in patients with advanced/recurrent cervical carcinoma.MethodsA retrospective review of medical records of recurrent cervical cancer patients, who had failed a previous platinum–paclitaxel treatment and received oral capecitabine 1250 mg/m2 twice daily continuously from day 1 to day 14 every 21 days, was performed from December 2013 to March 2018 at the Gynecologic Oncology Unit of the Fondazione IRCCS National Cancer Institute of Milan, Italy. The response rate was evaluated every three cycles according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Common Terminology Criteria for Adverse Events version 4.0 were used to evaluate adverse events.ResultsWe retrospectively analyzed 35 patients with recurrent cervical carcinoma, treated with oral capecitabine. All patients had previously received and failed a combination of carboplatin plus paclitaxel as first-line therapy for advanced/recurrent disease. Median age at the first capecitabine administration was 53 years (range 27–82). All patients were evaluable for response: the overall response rate was 34.2% (2.8% complete responses and 31.4% partial responses) with a clinical benefit rate of 57% (overall response rate plus 22.8% stabilizations of disease). The most common grade 1–2 adverse events per patient were fatigue (71.3%), hand-foot syndrome (57.0%), diarrhea (31.3%), constipation (17.0%), and nausea (10.4%). Only three patients (8.5%) reported grade 3 adverse events.ConclusionsOur data suggest that oral capecitabine should be considered an active and safe treatment in patients with recurrent cervical carcinoma after platinum failure. Based on these results, we consider capecitabine as warranting further clinical evaluation.

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Cardiac Biomarkers Predict for Ability To Tolerate and Complete Therapy with Lenalidomide ± Dexamathosone in AL Amyloidosis.

Blood ◽

10.1182/blood.v108.11.130.130 ◽

2006 ◽

Vol 108 (11) ◽

pp. 130-130 ◽

Cited By ~ 8

Author(s):

Angela Dispenzieri ◽

Martha Lacy ◽

Steven Zeldenrust ◽

Suzanne R. Hayman ◽

Shaji Kumar ◽

...

Keyword(s):

Adverse Events ◽

Overall Response Rate ◽

Response Rate ◽

Troponin T ◽

Single Agent ◽

Cardiac Biomarkers ◽

Al Amyloidosis ◽

Significant Activity ◽

Cardiac Biomarker ◽

Overall Response

Abstract Background: Primary systemic amyloidosis (AL) is an incurable plasma cell disorder. Lenalidomide, especially in conjunction with dexamethasone, has been shown to be highly active in patients with multiple myeloma. Methods: We studied the toxicity and efficacy of lenalidomide in patients with symptomatic AL. Patients received single agent lenalidomide. If progression by 3 months or no evidence of hematologic response after 3 cycles, dexamethasone was added. Originally, twenty-three patients (Cohort 1) were enrolled according to study design. Because of a significant early drop out rate and notable activity of the regimen, the trial was modified to include an additional 15 patients (Cohort 2). Baseline characteristics and adverse events are available for all enrolled patients, but at the time of this writing, response data are available for Cohort 1 patients due to short follow-up of Cohort 2, but will be updated by the time of the meeting. Results: Median age was 64 years, with 69% male. Twenty-three were previously treated. Organ involvement was cardiac (67%), renal (64%), hepatic (17%), nerve (17%). Thirty-three, twenty-two, and forty-four percent of patients were cardiac biomarker stage 1, 2, and, 3 respectively. Of the 37 patients, one was a cancel, and 6 have not yet made it through 3 months of protocol treatment and event monitoring. The respective median follow-ups for Cohorts 1 and 2 are 17 and 3.4 months. Of the remaining, 30 patients, within the first 3 cycles of therapy fifteen patients discontinued treatment: 7 early deaths and 8 adverse events or other causes. Three additional patients died 0.5 to 2 months after stopping treatment. The best predictor for early withdrawal and/or death was baseline NT-proBNP and cardiac biomarker staging system (cut-offs for serum troponin T <0.035 ng/ml and NT-proBNP <332 pg/ml--Stage I neither above cut-off; Stage III, both above cut-off; and Stage II, one above cut-off). Figure1 Figure1. Figure 2 Figure 2. Of the twenty 22 patients assessed for response ten patients responded to treatment for an overall response rate of 45%, including 23% organ responders. Among the patients with organ responses, there were four renal responses, two cardiac responses and two liver responses. All but one of the responders had dexamethasone added to their treatment program. The most common grade 3−4 adverse events at least possibly attributable to lenalidomide were neutropenia (38%), thrombocytopenia (21%), fatigue (15%), and rash (12%). Conclusions: Lenalidomide and dexamethasone has significant activity in patients with AL with an overall response rate of 45%. Baseline NT−proBNP may be an effective eligibility screening strategy for subsequent trials.

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A Phase I/II Trial of Bortezomib, Low Dose Intravenous Melphalan and Dexamethasone for Patients with Relapsed Multiple Myeloma.

Blood ◽

10.1182/blood.v108.11.3542.3542 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3542-3542 ◽

Cited By ~ 6

Author(s):

Rakesh Popat ◽

Catherine Williams ◽

Mark Cook ◽

Charles Craddock ◽

Supratik Basu ◽

...

Keyword(s):

Multiple Myeloma ◽

Phase I ◽

Median Time ◽

Low Dose ◽

Overall Response Rate ◽

Response Rate ◽

Chemotherapeutic Agents ◽

Time To Progression ◽

Overall Response ◽

Grade 3

Abstract Background: Bortezomib is an effective treatment for patients with relapsed multiple myeloma with an overall response rate (MR+PR+CR) of 46% and time to progression of 6.2 months (APEX study). We and others have previously demonstrated potent in-vitro synergy with chemotherapeutic agents such as melphalan and it is likely that this will translate into improved responses in the clinical setting. Methods: This was a multi-centre, non-randomised Phase I/II clinical trial for patients with relapsed multiple myeloma. Bortezomib 1.3mg/m2 was given on Days 1,4,8 and 11 of a 28 day cycle, and intravenous melphalan on Day 2 for a maximum of 8 cycles. In the Phase I component melphalan was given at 2.5, 5,7.5 and 10mg/m2 in a dose escalation scheme and the maximum tolerated dose (MTD) of 7.5mg/m2 was taken forward to an expanded Phase II component. Dexamethasone 20mg on the day of and the day after each dose of bortezomib was permitted for progressive or stable disease after 2 or 4 cycles respectively. Responses were classified by EBMT criteria. Results: To date 39 patients have been enrolled (median age 61years [range 40–77]) with a median of 3 lines of prior therapy [range 1–5] of which 26 (67%) have had one previous autologous stem cell procedure and 4 (10%) have had two. 23 (59%) have had prior exposure to thalidomide and 4 (10%) to bortezomib. 36 have now completed at least 1 cycle and are therefore evaluable for response. The overall response rate (CR+PR+MR) across all treatment levels was 75% rising to 81% (CR 11%; nCR 3%; VGPR 8%; PR 39%; MR 19%) with the addition of dexamethasone in 13 cases for suboptimal response. Rapid responses were seen with the median time to response being 1 month [range 1–6]. The median time to progression is 10.1 months and the median overall survival has not yet been reached at a median follow-up of 7.4 months. Of the patients that have had disease progression 7 (35%) had responses of longer duration than their previous therapy. The MTD was defined by unacceptable delays in administering treatment due to myelosuppresion. The toxicities have been acceptable with 13 SAEs reported of which 8 were hospitalisation due to infection. The most common grade 3–4 adverse events were: thrombocytopenia (53%), infections (25%), neutropenia (17%) and neuropathy (17%). Three grade 3 cardiac events were seen (myocardial infarction, atrial fibrillation and cardiac failure) and GCSF was administered to 13 patients as treatment and prophylaxis of grade 4 neutropenia. 13 patients were withdrawn from the study due to toxicity of which 7 were for neuropathy and 3 for delayed haematological recovery. Of note, 11 patients (28%) had pre-existing grade 1 neuropathy prior to starting therapy. Summary: The combination of bortezomib, low dose intravenous melphalan and dexamethasone appears to be highly effective in patients with relapsed multiple myeloma where a response rate of 81% is seen with 14% achieving nCR/CR. The toxicity profile associated is predictable, manageable and predominantly haematological. Recruitment is ongoing to a total of 53 patients.

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FINAL Results of an Phase, Multicenter, Randomied, Controlled OPEN LEVEL Trial: Decitabine Therapy in Patients with Myelodysplastic Syndromes

Blood ◽

10.1182/blood-2018-99-116041 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3865-3865

Author(s):

Zonghong Shao ◽

Hui Liu ◽

Hao Jiang ◽

Hongyan Tong ◽

Ruixiang Xiang ◽

...

Keyword(s):

Clinical Trials ◽

High Risk ◽

Adverse Events ◽

Myelodysplastic Syndromes ◽

Overall Response Rate ◽

Response Rate ◽

Conflicts Of Interest ◽

Study Drug ◽

Overall Response ◽

To Receive

Abstract Background: DNA hypomethylating agent, decitabine, has become the current standard therapy for patients with higher-risk myelodysplastic syndromes (MDS). Decitabine was launched in China in August 2009 without clinical trials. According to some retrospective studies, the efficacy and safety are similar to those reported in other countries, but there is still a lack of large-scale prospective clinical trials. So we start a prospective clinical trial in China to compare the effect and safety of decitabine in MDS, which was registered at clinicaltrials.gov (NCT02013102). Design: Adults with intermediate or high risk MDS by the International Prognostic Scoring System (IPSS≥0.5) were randomized to receive either decitabine 20 mg/m2 IV daily for 5 days (arm Ⅰ) or decitabine 12 mg/m2 IV daily for 8 days (arm Ⅱ) every four weeks. Patients continued to receive study drug for 4 cycles until death, disease progression, intercurrent illness preventing further administration of treatment, unacceptable adverse event or decision by the patient to withdraw from the study. And supportive care were permitted. The primary end point was overall response rate (ORR, CR+mCR+PR) by International Working Group (IWG 2006) criteria, secondary end points included CR, mCR, PR, HI, safety, et al. Results: We enrolled a total of 198 patients between 8/2013 and 12/2017, among which 7 patients didn't take decitabine, and 191 were included in the analysis. 94 in arm Ⅰ recieved decitabine and 97 in arm Ⅱ. 32.8% of patients withdrew from the study for a variety of reasons, including progression and death (5.1%), personal decision (13.6%), adverse events (6.6%), and other causes (7.6%). The median age of patients in arm Ⅰ was 54.88 years old and 54.82 years old in arm II. The median follow-up was 106 days for patients in both arms. The patients received a mean 2.5 cycles of decitabine therapy for arm Ⅰ and 2.0 cycles for arm Ⅱ. The overall response rate was 39.3% in total, and 41.5% and 38.1% (p=0.6598) for patients in arm Ⅰ and arm Ⅱ, respectively. And CR was 18.1% and 14.4% (p= 0.5584) , PR was 6.4% and 3.1% (p=0.3257) , mCR was 17.0% and 20.6% (p=0.5814) , HI was 3.2% and 1.0% (p=0.3633) , for patients in armⅠand armⅡ, respectively (Table 1). Among all patients, 38.7% were intermediate-1 risk, 40.3% were intermediate-2 risk, 20.4% were high risk. Analysis of response by MDS patient subtypes is shown in Table 2. Those who were higher risk experienced higher ORR and CR, while the difference is not significant between two arms (p>0.05). As expected, cytopenias were the most frequent complications (76.4%). Grade 3-4 neutropenia, thrombocytopenia and anemia considered to be at least possibly related to the study drug occurred at rates of 23.0%, 34.6%, and 34.6% of patients, respectively. Nonhematologic adverse events were also common including abnormal metabolism and nutrition (23.40% vs 18.56%), abnormal gastrointestinal function (29.79% vs 41.24%), cardiac disorders (11.70% vs 14.43%), infection and infectious diseases (32.98% vs 36.08%), abnormal skin and subcutaneous tissue and so on, which were no significant differences between two ams. During the study there were 17 SAE, only 7 cases were possibly related to drug therapy, such as pulmonary infection, Sepsis, myelosuppression, intracranial hemorrhage, hepatic failure, and arrhythmia. Conclusions: The use of 5-day and 8-day schedule decitabine is safe and effective in patients with intermediate and high risk MDS, among which there was no significant differences. Disclosures No relevant conflicts of interest to declare.

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Phase II: Combination of cladribine, cyclophosphamide, mitoxantrone, rituximab (R-CCM) in patients with relapsed and refractory follicular and mantle cell lymphoma, results of a prospective study at Kitasato University

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18542 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18542-18542 ◽

Cited By ~ 1

Author(s):

Y. Suzuki ◽

M. Danbara ◽

M. Hayama ◽

T. Togano ◽

M. Ohsaka ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Overall Response Rate ◽

Response Rate ◽

Cell Lymphoma ◽

Hemorrhagic Cystitis ◽

Single Agent ◽

Left Ventricular ◽

Overall Response ◽

Mantle Cell ◽

Grade Iii

18542 Background: Indolent non-Hodgkin’s lymphoma (I-NHL) account for 20% of all of NHL in Japan, and they are increasing in number. More than 80% of the patients who achieve a complete remission with the initial treatment, will require salvage therapy. Recently, cladribine (2-CdA), a purine analogue is receiving much attention, because, even as a single agent, it has shown a high efficacy for I-NHL. The aim of our study was to determine the effectiveness and toxicity of combined chemotherapy consisting of 2-CdA, cyclophosphamide (CYP), mitoxantrone (MIT), rituximab (R-CCM) in the treatment of refractory or relapsed I-NHL. Methods: Patient eligibility criteria were: Previously treated patients with I-NHL, refractory or relapsed disease, no chemotherapy or irradiation within 4 weeks prior to the study, life expectancy of at least 3 months, age: 20–75, perfomance status of 0–3, adequate function ( bone marrow, liver, kidney, lung, heart) and written informed consent. The treatment regimen was: 2-CdA given at a dose of 0.09 mg/kg/day in a 2-h intravenous infusion from day 2–4, CYP 200 mg/m2/day from day 2–4, MIT 8 mg/m2/day on day 2 and rituximab 375 mg/m2/day on day .Primary end point was overall response rate. Results: 9 patients were enrolled, 7 (2 with mantle cell lymphoma, MCL; and 5 with follicular lymphoma, FL) were eligible. Mean Age was 63(51–72). The mean observation time was 121 days(47–314). Overall response rate (complete and partial) just after this therapy was 85.7%, one was progressive disease. One of PR one relapsed and died ten months after this regimen. The major toxicity was myelosuppression. Grade-III and -IV neutropenia was seen in 7 patients, grade-III thrombocytopenia in one and grade-III hemorrhagic cystitis in one, but all of them recovered from these toxicity. After the treatment, Grade-IV pneumonia and grade-III left-ventricular diastolic dysfunction was seen in the PD patient and passed away. Conclusions: the R-CCM is effective and safe in a combined regimen for relapsed and refractory I-NHL patients. We have just begun this new regimen, therefore, further investigations with larger population are warranted. No significant financial relationships to disclose.

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Long-term disease control with capecitabine in advanced breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e12566 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e12566-e12566

Author(s):

Giovanna Masci ◽

Emanuela Ferraro ◽

Rosalba Torrisi ◽

Laura Giordano ◽

Monica Zuradelli ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Disease Control ◽

Overall Response Rate ◽

Response Rate ◽

Active Agent ◽

Advanced Breast ◽

Overall Response ◽

Metastatic Setting

e12566 Background: Capecitabine is an active agent in the treatment of advanced breast cancer (ABC). It is commonly administered at the approved dosage of 1250 mg/m2 twice daily for 2 weeks followed by 1 week rest period. Methods: The study population included 162 pts retrospectively analyzed with ABC treated with capecitabine between 2006 and 2015 at our Institute. Capecitabine was given 14 day on,7 day off cycle at a daily dose of 1900 mg/m2, a modified schedule used to minimize side effects. The objective were overall response rate (ORR), median duration of treatment (MDT) progression-free survival (PFS), overall survival (OS). Results: The median age was 64 years (range 33-89). Pts with hormone receptor positive ABC were 133 (82%), 6 (4%) had HER-2 positive disease and 29 (18%) a triple negative profile. One hundred and thirty eight (85%) had already received chemotherapy in adjuvant and/or metastatic setting; anthracycline and taxanes were given in 64 pts (40%), anthracycline in 60 pts (37%) and taxane in 4 pts (2%), 9 pts (6%) received other regimens of chemotherapy. Twenty-five pts (15%) were chemo-naive. One hundred and thirty-three pts (82%) received endocrine therapy. Sixty-four pts (38%) had predominantly non-visceral metastases, 26 pts (16%) exclusive visceral involvement, 72 (44%) exhibited both characteristics. ORR was 58% (CR = 2%, PR = 16% SD = 40%) and MDT was 6.9 months. The median PFS and OS were 6.9 months and 21 months, respectively. We defined as “long responders” 19 pts (12%) with disease control interval > 24 months and, among them, as “very long responders”, 9 pts (6%) who exceeded 36 months. Efficacy was unrelated to biological profiles, sites of metastasis or previous therapies. No grade 3 and 4 adverse events occurred. Conclusions: Our results show that in pts with ABC a lower dose of capecitabine has a good toxicity profile and similar overall response rate and survival data in comparison to the approved dose. In addition, we identified a subset of long and very long responders but further studies are warranted to evaluate clinical/biological predictors of a long-term response.

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Bortezomib, Rituximab, and Dexamethason (BORID) as Salvage Treatment in Relapsed/Refractory Mantle Cell Lymphoma: Sustained Disease Control in Patients Achieving a Complete Remission.

Blood ◽

10.1182/blood.v110.11.2578.2578 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2578-2578 ◽

Cited By ~ 2

Author(s):

Johannes Drach ◽

Hannes Kaufmann ◽

Oskar Pichelmayer ◽

Verena Sagaster ◽

Sonja Holzer ◽

...

Keyword(s):

Adverse Events ◽

Disease Control ◽

Mantle Cell Lymphoma ◽

Overall Response Rate ◽

Response Rate ◽

Cell Lymphoma ◽

High Dose ◽

Synergistic Activity ◽

Overall Response ◽

Mantle Cell

Abstract Background: Bortezomib (B) belongs to a new class of anti-cancer agents, the proteasome inhibitors, and has documented activity in multiple myeloma and mantle cell lymphoma (MCL). Preclinical studies suggest that B has synergistic activity with rituximab (R), which provides a rationale for the exploration of treatment combinations. We therefore evaluated the activity and safety of B in combination with R and dexamethasone (BORID) in patients with relapsed and refractory MCL (phase II trial). Methods: A treatment cycle consists of B at 1.3 mg/m2 administered on days 1, 4, 8, and 11, R at 375 mg/m2 administered on day 1, and dexamethasone 40 mg orally on days 1 to 4. Cycles are repeated every 3 weeks for a total of 6 treatment cycles. Patients (pts) achieving a response received 4 additional doses of R as maintenance (every 8 weeks). Pts with progressive MCL after at least one prior line of therapy (including CHOP or a CHOP-like regimen) were eligible. Results: We have completed enrollment of 16 pts (median age, 67 years; range, 48 to 75 years) after a median of 3 lines of prior therapies (range, 1 to 6, prior rituximab in 88%; thalidomide in 50%; high-dose therapy in 31%; a fludarabine-containing regimen in 31%). Median time between start of frontline therapy and study inclusion was 42 months (range, 11 to 98 months). Severe adverse events (> grade II) included infections (herpes zoster in 2 pts, bacterial pneumonia, mucosal candidiasis), peripheral neuropathy (3 pts), fatigue (2 pts) and vasculitic skin infiltrates in 3 pts. Thrombopenia (< 50 G/L) occured in 2 pts. All adverse events were managable by standard means of supportive care and prolongation of the treatment interval between cycles. Overall response rate was 69% (11 of 16 pts), with 6 pts achieving a CR (38%; confirmed by PET-scan in 5 pts) and 5 pts reaching a PR. Skin infiltrates (histologically proven T-cell infiltrates) preceded achievement of CR in 2 pts. Remission status appeared to be associated with progression-free survival (PFS): Patients in CR had longer PFS (29+, 24+, 21+, 12+, 12, and 10+ months) compared to patients in PR (median 8.5 months, range 6 – 15). Conclusions: BORID has promising activitiy (69% overall response rate; CR rate 38%) and managable toxicity in this patient population with predominantly heavily pretreated MCL. Achievement of a CR emerged as an important factor for sustained disease control. Further evaluation of this regimen, in particular in pts at an earlier phase of the disease, is warranted.

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AOP2014, a Novel Peg-Proline-Interferon Alpha-2b with Improved Pharmacokinetic Properties, Is Safe and Well Tolerated and Shows Promising Efficacy in Patients with Polycythemia Vera (PV)

Blood ◽

10.1182/blood.v120.21.175.175 ◽

2012 ◽

Vol 120 (21) ◽

pp. 175-175 ◽

Cited By ~ 3

Author(s):

Heinz Gisslinger ◽

Robert Kralovics ◽

Bettina Gisslinger ◽

Daniel Lechner ◽

Veronika Buxhofer-Ausch ◽

...

Keyword(s):

Adverse Events ◽

Phase I ◽

Research Funding ◽

Overall Response Rate ◽

Response Rate ◽

Phase Iii ◽

Molecular Response ◽

Overall Response ◽

Long Term Treatment

Abstract Abstract 175 AOP2014 is a next generation long-acting pegylated IFNa-2b, consisting predominantly of only one isoform, as opposed to other commercially available pegylated interferons. AOP2014 has a distinct pharmacokinetic and pharmacodynamic profile which may potentially allow reduced dosing frequencies compared to other pegylated IFNs. This is being expected to result in improved tolerability, better compliance, and, finally, favorable long-term treatment outcomes. AOP2014 is a designated Orphan Drug in EU for treatment of patients with PV. The maximum tolerated dose (MTD), long term safety and efficacy of AOP2014, administered subcutaneously every 14 days, are the main objectives of the study. Patients with confirmed PV diagnosis, age equal or older 18 years, both naïve and cytoreduction pre-treated are eligible. After establishing the MTD, an extended cohort of 25 additional patients was planned to be recruited. European LeukemiaNet criteria were used for response assessment. 34 patients, treated by March 31, 2012 were included into this analysis: 25 in Phase I (dose-finding) and 9 in the Phase II (cohort extension). Median time from diagnosis was 24 months (range 0–180). 12 patients (35%) were HU pre-treated (mean past duration of HU pre-treatment 39 months, mean daily HU dose 950 mg). Median number of phlebotomies in the past 3 months prior to inclusion was 1 (range 0–8), a total of 21 patients (62%) were regularly phlebotomized at least once in three months prior to study entry. 11 patients (32%) had a history of thrombotic complications. Median Hct at baseline was 42% (range 36–51). Median WBC and platelet counts were 10.6*109/l (range 3.9–20.4) and 452*109/l (range 141–1019), respectively. 17 patients (50%) had splenomegaly at baseline. The median reported treatment duration was 41 weeks (range: 1 day – 80 weeks), 11 patients completed 1 year on treatment. Doses from 50 to 540 ug every two weeks were tested, 540 ug has been concluded as MTD as the highest tested dose, since no DLTs occurred in the study. The mean administered dose (both Phase I and II patients) was 287 ug. After 28 weeks of treatment (21 evaluable patients), 71% of patients had hematological response (7 CR, 33%; 8 PR, 38%), at week 36 (19 evaluable patients) 8 patients (42%) achieved a CR and 8 patients (42%) a PR, overall response rate (ORR, CR+PR) was 84%. At week 52 (1 year; 11 evaluable patients), 5 patients (46%) had CR and 5 (46%) PR, ORR was 91%; 8 (73%) patients presented with completely normalized blood values, all evaluable patients were phlebotomy free at this timepoint. 4 patients (of 12 evaluable for this measurement, 33%) had still enlarged spleen at week 52. At week 76, 2 evaluable patients were complete responders. At week 52, 1 patient (of 9 evaluable, 11%) developed partial molecular response, at week 68 3 patients (of 7 evaluable, 43%) had partial molecular response. One patient with allelic burden of 22% at baseline developed complete molecular response at week 36 (still ongoing). Mainly grade 1 and 2 adverse events were reported. A total of 358 adverse events occurred. 27 patients (79%) suffered from drug-related adverse events. 9 patients (26%) developed serious adverse events; 4 SAEs were considered to be treatment related. 5 patients (15%) discontinued their study participation prematurely, 3 of them due to adverse events (deterioration of underlying disease and two cases of depression). Acceptable tolerability and durable clinical benefits have been demonstrated in PV patients measured as overall response rate of above 90% with CRs of 46% at one year after treatment start. Phlebotomy independence and normalization of hematological parameters could be seen in most of the patients. The study continues to recruit and collect long term follow up information. Presented data support further development of AOP2014 in PV, a Phase III study is planned to start early 2013. Disclosures: Gisslinger: AOP Orphan Pharmaceuticals AG: Research Funding; Novartis: Speakers Bureau; Celgene Austria: Research Funding, Speakers Bureau. Kralovics:AOP Orphan Pharmaceuticals AG: Research Funding. Gisslinger:AOP Orphan Pharmaceuticals AG: Research Funding. Lechner:AOP Orphan Pharmaceuticals AG: Research Funding. Buxhofer-Ausch:AOP Orphan Pharmaceuticals AG: Research Funding. Strecker:AOP Orphan Pharmaceuticals AG: Research Funding. Gastl:AOP Orphan Pharmaceuticals AG: Research Funding. Willenbacher:AOP Orphan Pharmaceuticals AG: Research Funding. Greil:AOP Orphan Pharmaceuticals AG: Research Funding. Egle:AOP Orphan Pharmaceuticals AG: Research Funding. Melchardt:AOP Orphan Pharmaceuticals AG: Research Funding. Burgstaller:AOP Orphan Pharmaceuticals AG: Research Funding. Schloegl:AOP Orphan Pharmaceuticals AG: Research Funding. Tarmann:AOP Orphan Pharmaceuticals AG: Employment. Zoerer:AOP Orphan Pharmaceuticals AG: Employment. Klade:AOP Orphan Pharmaceuticals AG: Employment. Zahriychuk:AOP Orphan Pharmaceuticals AG: Employment. Thaler:AOP Orphan Pharmaceuticals AG: Research Funding.

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