NCCTG N057K phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: A North Central Cancer Treatment Group trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2031-2031
Author(s):  
Daniel Ma ◽  
Evanthia Galanis ◽  
David Schiff ◽  
Wenting Wu ◽  
Patrick J. Peller ◽  
...  
Keyword(s):  
Phase Ii ◽  
Residual Disease ◽  
Methylation Status ◽  
Mtor Inhibitors ◽  
Outcome Data ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Drug Induced ◽  
Flt Pet ◽  
Grade 3

2031 Background: The mammalian target of rapamycin (mTOR) functions within the PI3K/Akt pathway as a critical modulator of cell survival. Preclinical studies in GBM indicate that the combination of mTOR inhibitors, such as everolimus (RAD001), with either radiation therapy (RT) or temozolomide (TMZ) provide increased tumor cell killing. Methods: Newly diagnosed GBM pts were eligible for the study. RAD001 was dosed orally at 70 mg/week weekly, starting 1 week prior to RT/TMZ, and continued throughout RT/TMZ, adjuvant TMZ and then until progression. This was a single arm phase II design powered to detect a true overall survival at 12 months (OS12) of 73% (vs 58% in historical controls). Secondary endpoints were toxicity, response rate, and time to progression (TTP). A subgroup of patients with measurable residual disease were eligible for the PET imaging component of the study, consisting of an 18FLT-PET/CT scan performed before and after the initial two doses of RAD001 but before the first dose of RT or TMZ. Results: 103 patients were accrued to phase II of which 100 were evaluable. The median age was 60.5 years (23-81), median ECOG PS was 1, 46 patients had GTR, 33 STR, and the remainder had biopsy at diagnosis. Treatment tolerance was acceptable: 17% patient had at least one grade 3 hematologic toxicity; 14% had at least one grade 4 hematologic toxicity, 42% had at least one grade 3 non-heme toxicity, while 12% had at least one grade 4 non-heme toxicity. No increased incidence of infectious complications was observed and there were no treatment related deaths. Median PFS was 5.3 months (1.3-21.4), with 22 patients progression free. Mature OS data will be available at the meeting. MGMT methylation status analysis is ongoing. Of the pts who had evaluable FLT-PET data, three of eight (37.5%) had a drop in SUVmax >25% after two treatments of RAD001. Conclusions: RAD001 with standard of care chemoradiation had moderate toxicity. Serial 18FLT-PET was feasible for evaluating drug-induced changes in tumor proliferation following RAD001. Final outcome data and association of MGMT status with outcome will be reported at the meeting.

Safety and effectiveness of dose dense neoadjuvant chemotherapy in patients with stage II/III breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10622-10622
Author(s):  
S. A. McDaniel ◽  
H. Krontiras ◽  
J. T. Carpenter ◽  
L. M. Nabell ◽  
K. I. Bland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
Dose Dense ◽  
To Receive

10622 Background: NSABP B-18 randomized women with operable breast cancer to receive chemotherapy either pre- or postoperatively; OS and DSF rates at 9 years were identical. Importantly, pathologic complete response (pCR) was directly proportional to DFS and OS. Recently, dose dense adjuvant chemotherapy has shown a statistically significant improvement in DFS and OS. However, no data is available for the use of dose dense preoperative chemotherapy at this time. Methods: Women enrolled in the I-SPY correlative trial with newly diagnosed breast cancer, T ≥ 3cm, any N, M0 were evaluated to assess response rates and safety to dose dense neoadjuvant chemotherapy (doxorubicin 60 mg/m2 IV Q2 wks × 4, paclitaxel 175 mg/m2 IV Q2 wks × 4, and cyclophosphamide 600 mg/m2 IV Q2 wks × 4). Results: Since 02/2003, 43 pts have been treated with dose dense neoadjuvant chemotherapy on the I-SPY trial at UAB (mean age 47.9). 47% of the pts were ER+, 37% were PR+ and 5% were Her2+ by FISH. 2 pts dropped out for personal reasons and 9 pts are actively undergoing treatment. Overall, 32 pts received dose dense chemotherapy and proceeded to surgery. Of those, 31 received dose dense sequential ATC and 1 received dose dense concurrent AC followed by T. 34% had a pCR (breast & nodes) while an additional 10% had a pCR in the breast but residual disease in lymph nodes; 41% had a PR; 9% had SD; and 6% had PD. Hematologic toxicity consisted of grade 3 anemia in 2 pts, febrile neutropenia in 2 pts and no grade 4 thrombocytopenia. Non-hematologic grade 3–4 toxicity consisted of mediport-associated thrombosis in 2 pts, hyperglycemia in 2 pts, syncope in 1 pt, neuropathy in 1 pt, and disseminated varicella in 1 pt. Conclusion: Our results show that dose dense neoadjuvant chemotherapy achieves a pCR (breast & nodes) in about 1/3 of patients (34%) with tolerable toxicity. No significant financial relationships to disclose.

Phase II Clinical and Correlative Study Of Carfilzomib, Lenalidomide, and Dexamethasone Followed By Lenalidomide Extended Dosing (CRD-R) Induces High Rates Of MRD Negativity In Newly Diagnosed Multiple Myeloma (MM) Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 538-538 ◽  
Author(s):  
Neha Korde ◽  
Adriana Zingone ◽  
Mary L Kwok ◽  
Elisabet E. Manasanch ◽  
Manisha Bhutani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Combination Therapy ◽  
Phase Ii ◽  
Plasma Cells ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Color Flow ◽  
Time Points ◽  
Grade 3

Abstract Background An irreversible proteasome inhibitor with decreased peripheral neuropathy compared to bortezomib, Carfilzomib (Cz) has potent anti-MM effects resulting in deep clinical responses and durable remissions. In this two-stage phase II trial of 45 planned patients, we treat newly diagnosed MM patients with Cz, lenalidomide(Ln), and dexamethasone (Dx) followed by 2 years of Ln maintenance. Methods Eight 28-day cycles of combination therapy comprises: Cz IV 20/36 mg/m2 on days 1, 2, 8, 9, 15, 16; Ln oral 25 mg days 1-21; and Dx IV or oral 20/10 mg (C1-4/5-8) on days 1, 2, 8, 9, 15, 16, 22, 23. Transplant eligible patients undergo stem cell collection after 4 cycles of CRd and continue with treatment. After 8 cycles of combination therapy, patients with SD or better receive up to 24 cycles of Ln extended dosing 10 mg days 1-21. Primary endpoint is ≥ grade 3 neuropathy. Bone marrow samples are collected at baseline, C1D2 (single agent Cz exposed), CR/end of cycle 8 (cycles 1-8), CR/end of cycle 20 (cycles 9-20), and CR/end of cycle 32/treatment termination (cycles 21-32). Patients are evaluated for clinical biomarkers, FDG-PET CT, and MRD studies (flow cytometry and PCR) at regular time points. Flow cytometry utilizes 8-color flow panel and analyzes ≥ 3 x 106 events (sensitivity 1 x 10-5). Results Forty-one patients meeting eligibility criteria have been enrolled (24 male, 17 female; median age 60; range 40-88). Among patients enrolled, median M-spike is 2.9 (1.0-7.6 g/dL) and isotypes included 26-IgG, 10 – IgA, 4 – free kappa, and 1 – free lambda. Thirty-eight patients are evaluable for response and toxicity. No patients have had ≥ grade 3 neuropathy. The mean decline in serum M-protein (n=33) was 72% after 1 cycle of CRd received. Best responses after a median of 9 cycles (range 2-20) completed, include 17–sCR/1-CR/6-nCR (63%), 10-VGPR (26%), 3-PR (8%), and 1-SD (3%). Among 18/38 (47%), median time to sCR/CR was 5 cycles. Among 14 CR/sCR + 3 nCR patients who underwent MRD assessment, all were negative. Among patients with ≤ VGPR at the end of 8 cycles of CRd, 5/8 (63%) had evidence of immunophenotypically abnormal plasma cells defined by flow cytometry, and 3 patients had undetectable abnormal plasma cells (1 achieved sCR after 8 additional Ln cycles). After median follow-up of 10 months (3-22), PFS rate was 83.3%. Twenty-five patients have completed 8 cycles of CRd, while 24/25 continued to Ln extension and 1 patient opted to exit study after CRd. Patients with non-hematologic toxicity events (≥ grade 3) include: electrolyte disturbances - 7(18%), LFT elevation - 5(13%), rash/pruritus – 4(11%), fatigue – 4(11%), cardiovascular – 3(8%), dyspnea/respiratory – 3(8%), constitutional symptoms – 2(5%), infections – 2(5%), VTE - 2(5%), and anxiety – 1(3%). Patients with hematologic toxicity events (≥ grade 3) include: lymphopenia –24(63%), anemia – 6(16%), leukopenia - 5(13%), and thrombocytopenia - 4(11%). All patients with baseline FDG avid lesions or extramedullary disease showed decrease or resolution of FDG avidity at MRD assessment time points. Conclusions Beyond traditional clinical response criteria, using a functional imaging and highly sensitive MRD assays, we consistently show high rates of deep remission and MRD negativity among newly diagnosed MM patients treated with carfilzomib, revlimid, dexamethasone (CRd) combination therapy. The results were very similar across age-groups and the oldest patient on this trial was 88 years old. If deep remissions are maintained with a delayed ASCT strategy incorporating extended dosing revlimid therapy, this may be a future strategy available to all patients irrespective of age. Disclosures: Off Label Use: Abstract is in newly diagnosed Multiple Myeloma patients. Carfilzomib is approved for relapsed/refractory patients.

scholarly journals ACTR-03. FINAL RESULTS OF A PHASE II STUDY OF HYPOFRACTIONATED RADIOTHERAPY WITH CONCURRENT AND ADJUVANT TEMOZOLOMIDE IN PATIENTS OVER 70 YEARS OLD WITH NEWLY DIAGNOSED GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi12-vi12
Author(s):  
Mehran Yusuf ◽  
Jeremy Gaskins ◽  
Shiao Woo ◽  
Eric Burton
Keyword(s):  
Phase Ii ◽  
Methylation Status ◽  
Progression Free Survival ◽  
Hypofractionated Radiotherapy ◽  
Newly Diagnosed ◽  
Linear Effect ◽  
Adjuvant Temozolomide ◽  
Kaplan Meier ◽  
Newly Diagnosed Glioblastoma ◽  
Grade 3

Abstract BACKGROUND We sought to determine the efficacy and tolerability of hypofractionated radiotherapy (HFRT), 34Gy given over two weeks with concurrent and adjuvant temozolomide, in patients over 70 years old with newly diagnosed GBM. METHODS Patients ≥ 70 years of age with newly diagnosed GBM received HFRT to a dose of 34 Gy in 10 fractions over 2 weeks, delivered with concurrent and adjuvant TMZ. Quality of life (QOL) data using the validated functional assessment of cancer therapy-brain (FACT-BR) questionnaire was collected. Kaplan-Meier methods and log-rank tests were used for survival analyses. A random intercepts growth model with baseline and linear effect in time terms was used to assess QOL with relation to protocol treatment. RESULTS Eleven patients were enrolled from 12/1/2015 to 2/5/2018. Median age and KPS of the cohort was 74 years (range 70 -81) and 80 (range 60–100). Eight patients have died. Median follow-up of the cohort was 13.8 months (range 3 – 26 months). The median progression free survival (PFS) was 6.0 months (CI 4.7 months -not achieved (NA) and the median overall survival (OS) was 24.5 months (CI 10.2 months –NA). MGMT methylation status was significantly associated with both PFS (p =0.02) and OS (p =0.02). All patients completed HFRT with no patients developing ≥ grade 3 adverse treatment events. QOL did not significantly worsen over time with therapy (p =0.75). CONCLUSIONS This completed phase II trial suggest a HFRT schedule of 34Gy delivered over 2 weeks with concomitant and adjuvant TMZ is well tolerated in elderly GBM patients without compromising clinical outcomes. This result compares favorably to the longer HFRT regimen of 40Gy over 3 weeks. ClinicalTrials.gov identifier: NCT01985087

A phase II trial of lithium, bevacizumab, temozolomide, and radiation for newly diagnosed glioblastomas (GBM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13033-e13033
Author(s):  
Ashwatha Narayana ◽  
Moses M Tam ◽  
Deborah Beth Gruber ◽  
John Golfinos ◽  
Erik Parker ◽  
...  
Keyword(s):  
Phase Ii ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Median Number ◽  
Hematological Toxicity ◽  
Newly Diagnosed ◽  
Goal Level ◽  
Field Radiation ◽  
Grade 3 ◽  
Involved Field

e13033 Background: Invasion is a dominant escape mechanism following angiogenic blockade in glioblastomas (GBM). Lithium has shown anti-invasive activity in glioma cells by inhibiting Glycogen Synthetase Kinase -3. This phase II study evaluated the safety and efficacy of using lithium and bevacizumab (BEV) in newly diagnosed GBM. Methods: From 2010 through 2012, 20 GBM patients with residual disease after surgery were treated with involved-field radiation therapy to 5940 cGy and concomitant temozolomide (TMZ) (75 mg/m2 daily for 42 days) along with BEV (10 mg/kg every 2 weeks), starting 29 days after surgery. This was followed by six 28-day cycles of TMZ (150 mg/m2 on days 1-7, BEV (10 mg/kg) on days 8 and 22, and lithium 300 mg BID. Lithium was increased every 7 days up to 600 mg BID with a serum lithium goal level of 0.8 to 1.2 mEq/L. Results: The median follow-up was 9.9 months (range 1.9-24.5). Fourteen patients (70.0%) received at least one dose of lithium and three patients completed the entire course of therapy. The median number of BEV infusion was 9 (range 2-19). Five patients discontinued trial due to skin sensitivity (n = 2), pulmonary embolism (n = 1), infection (n = 1), and hematological toxicity (n=1). Two patients experienced dose limiting lithium toxicity which included drowsiness (n = 1) and tremor (n = 1). No patients experienced grade 3/4 intra-cranial hemorrhage. The median progression free survival (PFS) was 9.3 months. The 12-month PFS and OS were 31.9% and 59.3% respectively. For the 14 patients who received lithium, the 12-month PFS and OS were 42.9% and 69.2% respectively. Conclusions: The strategy of targeting angiogenesis and invasion simultaneously in newly diagnosed GBM is effective and feasible. Clinical trial information: NCT01105702.

Phase II clinical and correlative study of carfilzomib, lenalidomide, and dexamethasone (CRd) in newly diagnosed multiple myeloma (MM) patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18568-e18568 ◽  
Author(s):  
Neha Korde ◽  
Adriana Zingone ◽  
Mary Kwok ◽  
Elisabet E. Manasanch ◽  
Manisha Bhutani ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Phase Ii ◽  
Fdg Pet ◽  
Single Agent ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Clinical Biomarkers ◽  
Pet Ct ◽  
Grade 3 ◽  
Fdg Pet Ct

e18568 Background: Carfilzomib (Cz) is an irreversible proteasome inhibitor with potent anti-MM effects and decreased peripheral neuropathy rates compared to bortezomib. In this two-stage phase II trial of 45 planned patients, we treat newly diagnosed MM patients with Cz, lenalidomide(Ln), and dexamethasone (Dx). Methods: Eight 28-day cycles of induction comprises of Cz IV 20/36 mg/m2 on days 1, 2, 8, 9, 15, 16; Ln oral 25 mg days 1-21; and Dx IV/oral 20/10 mg on days 1, 2, 8, 9, 15, 16, 22, 23. Transplant eligible patients undergo stem cell collection after 4 cycles of CRd and continue with induction. After 8 cycles of induction, patients with SD or better receive 12 cycles of Ln maintenance 10 mg days 1-21. Primary endpoint is ≥ grade 3 neuropathy. Bone marrow samples are collected at baseline, C1D2 (single agent Cz exposed), CR/end of cycle 8 (cycles 1-8), and CR/end of cycle 21 (cycles 9-21). Patients are evaluated for clinical biomarkers and MRD studies (flow cytometry, PCR, and FDG PET-CT) at regular time points. Results: Approximate enrollment rate is 1-2 patients/month. Six patients meeting eligibility criteria have been enrolled (2 male, 4 female; median age 58; age 42-74). Thus far, 5/6 patients are evaluable for toxicity and response (1-5 cycles, 2-4 cycles, 1-2 cycles, and 1-1 cycle). No patients have reported ≥ grade 3 neuropathy. Non-hematologic toxicity (≥ grade3) includes: 1 - LFT elevation and 1 - anxiety. One patient had ≥ grade3 hematologic toxicity with lymphopenia. After median 3 cycles of CRd, 3 patients achieved VGPR, 1 patient achieved PR, and 1 remained at SD. Mean decline in serum markers (M-protein or FLCs) was 87% (60-100%) among responders. One patient had 98% decline in FLCs after 1 cycle and a decrease in abnormal plasma cell burden to ≤ 2% by flow cytometry after 3 cycles. Updated results on additional patients and molecular/MRD studies (flow cytometry, PCR, and FDG PET-CT) will be presented at meeting. Conclusions: Combination therapy with CRd is a tolerable and effective regimen against upfront MM, evoking rapid and deep disease control.

scholarly journals Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia

2016 ◽  
Vol 34 (36) ◽  
pp. 4381-4389 ◽  
Author(s):  
Arend von Stackelberg ◽  
Franco Locatelli ◽  
Gerhard Zugmaier ◽  
Rupert Handgretinger ◽  
Tanya M. Trippett ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Recommended Dosage ◽  
Disease Response ◽  
Grade 3 ◽  
Minimal Residual

Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children < 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 µg/m2/d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 µg/m2/d for the first 7 days, followed by 15 µg/m2/d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade ≥ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.

Promising Survival for Patients With Newly Diagnosed Glioblastoma Multiforme Treated With Concomitant Radiation Plus Temozolomide Followed by Adjuvant Temozolomide

2002 ◽  
Vol 20 (5) ◽  
pp. 1375-1382 ◽  
Author(s):  
Roger Stupp ◽  
Pierre-Yves Dietrich ◽  
Sandrine Ostermann Kraljevic ◽  
Alessia Pica ◽  
Ivan Maillard ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Pneumocystis Carinii ◽  
Survival Rates ◽  
Concomitant Treatment ◽  
Newly Diagnosed ◽  
Open Label ◽  
Fractionated Radiotherapy ◽  
Adjuvant Temozolomide ◽  
Grade 3

PURPOSE: Temozolomide is a novel oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme (GBM). This phase II study was performed to determine the safety, tolerability, and efficacy of concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide therapy in patients with newly diagnosed GBM. PATIENTS AND METHODS: Sixty-four patients were enrolled onto this open-label, phase II trial. Temozolomide (75 mg/m2/d × 7 d/wk for 6 weeks) was administered orally concomitant with fractionated radiotherapy (60 Gy total dose: 2 Gy × 5 d/wk for 6 weeks) followed by temozolomide monotherapy (200 mg/m2/d × 5 days, every 28 days for six cycles). The primary end points were safety and tolerability, and the secondary end point was overall survival. RESULTS: Concomitant radiation plus temozolomide therapy was safe and well tolerated. Nonhematologic toxicities were rare and mild to moderate in severity. During the concomitant treatment phase, grade 3 or 4 neutropenia, thrombocytopenia, or both were observed in 6% of patients, including two severe infections with Pneumocystis carinii. During adjuvant temozolomide, 2% and 6% of cycles were associated with grade 3 and 4 neutropenia or thrombocytopenia, respectively. Median survival was 16 months, and the 1- and 2-year survival rates were 58% and 31%, respectively. Patients younger than 50 years old and patients who underwent debulking surgery had the best survival outcome. CONCLUSION: Continuous daily temozolomide and concomitant radiation is safe. This regimen of concomitant chemoradiotherapy followed by adjuvant chemotherapy may prolong the survival of patients with glioblastoma. Further investigation is warranted, and a randomized trial is ongoing.

A pilot study of topotecan in the treatment of serous carcinoma of the uterus

2003 ◽  
Vol 13 (2) ◽  
pp. 216-222
Author(s):  
J. T. Chambers ◽  
T. J. Rutherford ◽  
P. E. Schwartz ◽  
M. L. Carcangiu ◽  
S. K. Chambers ◽  
...  
Keyword(s):  
Pilot Study ◽  
Topoisomerase I ◽  
Residual Disease ◽  
Serous Carcinoma ◽  
Hematologic Toxicity ◽  
First Line ◽  
Uterine Serous Carcinoma ◽  
Grade 3 ◽  
Disease Free

A pilot study investigated topotecan (Hycamtin, GlaxoSmithKline, Philadelphia, PA), a topoisomerase I inhibitor, in treating uterine serous carcinoma, a typically unresponsive aggressive tumor. Fifteen patients were surgically staged, then treated with topotecan (1.5 mg/m2, Days 1–5 every 21 days) as first-line therapy (n = 12) or secondary to platinum failure (n = 3). Patients received topotecan through six courses, disease progression, or unacceptable toxicity. Grade 3/4 hematologic toxicity prompted dose adjustments. Thirteen patients exhibited no gross evidence of residual disease postoperatively. At topotecan initiation, one patient had 5-cm and one had < 1-cm residual disease. Seventy-eight courses (median, six) were administered; 12 (80%) patients completed the specified protocol. Common serious toxicities included grade 3 neutropenia (33%), anemia (13%), and thrombocytopenia (13%). Eight patients received erythropoietin and/or granulocyte colony-stimulating factor. Median follow-up for 14 evaluable patients was 26 months (range, 13–40). Of 11 evaluable first-line topotecan patients, nine were alive at follow-up; five were disease-free. Of three second-line topotecan patients, two died and one was alive with disease 31 months post-treatment. One patient with measurable disease achieved a complete and one a partial response as assessed by computed tomography scan. Median progression-free survival was 25 months; median survival has not been reached at 26 months. Although topotecan's antitumor activity cannot yet be quantified, disease-free interval and survival outcomes compare favorably with other therapies in uterine serous carcinoma. Further evaluation of topotecan in this population is warranted.

Multicenter Phase II Study of a 28-Day Regimen of Orally Administered Eniluracil and Fluorouracil in the Treatment of Patients With Anthracycline- and Taxane-Resistant Advanced Breast Cancer

2002 ◽  
Vol 20 (4) ◽  
pp. 987-993 ◽  
Author(s):  
Edgardo Rivera ◽  
Linda Sutton ◽  
Bruce Colwell ◽  
Mark Graham ◽  
Debra Frye ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Median Duration ◽  
Dihydropyrimidine Dehydrogenase ◽  
Advanced Breast ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Grade 3

PURPOSE: Eniluracil (776C85), a potent inactivator of dihydropyrimidine dehydrogenase, allows fluorouracil (5-FU) to be administered orally on a schedule that simulates continuous-infusion 5-FU. The primary objective of this study was to estimate the objective tumor response rate of orally administered eniluracil and 5-FU in the treatment of anthracycline- and taxane-resistant advanced breast cancer. PATIENTS AND METHODS: Patients with anthracycline- and taxane-resistant advanced breast cancer were enrolled onto this open-label, phase II, multicenter study. Patients received orally administered 5-FU 1.0 mg/m2 with eniluracil given in a 10:1 ratio (eniluracil:5-FU) twice daily for the first 28 days of each 35-day cycle. RESULTS: Eighty-four patients were enrolled. Eight partial responses were observed in 84 patients (10%; 95% confidence interval [CI], 4.2% to 17.9%), and 20 patients (24%) had stable disease. The median duration of partial response was 20.1 weeks (95% CI, 12 to 26.7 weeks). The median duration of progression-free survival and overall survival for all patients was 9.9 weeks and 40.4 weeks, respectively. Most adverse events were grade 1 or 2 in intensity. Diarrhea, nausea, malaise/fatigue, vomiting, and mucositis were the most common treatment-related nonhematologic adverse events. The most frequently occurring grade 3 or 4 treatment-related adverse events were malaise/fatigue and diarrhea, occurring in 17% and 7% of patients, respectively. The incidence of grade 3 or 4 hematologic toxicity was low. Grade 3 or 4 hyperbilirubinemia occurred in 17% of patients. CONCLUSION: Eniluracil–5-FU has modest antitumor activity and an acceptable safety profile in anthracycline- and taxane-resistant breast cancer. Treatment was convenient, and patient compliance was high.

scholarly journals CTNI-43. ANLOTINIB COMBINED WITH STUPP REGIMEN IN TREATING PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME: A PHASE II PILOT STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii52-ii52
Author(s):  
Shuzhen Lai ◽  
Yuanyuan Chen
Keyword(s):  
Pilot Study ◽  
Glioblastoma Multiforme ◽  
Adjuvant Therapy ◽  
Disease Progression ◽  
Phase Ii ◽  
Signal Pathways ◽  
Severe Toxicity ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma ◽  
Grade 3

Abstract PURPOSE Anlotinib, an orally multi-target tyrosine kinase inhibitor, inhibits tumor angiogenic and proliferative signal pathways. We performed a phase II trial of anlotinib in combination with the STUPP regimen in patients with newly diagnosed glioblastoma multiforme（GBM）to determine whether the combination therapy would safely improve outcomes in this group of patients. An initial pilot study assessed interim safety and tolerability. METHODS AND MATERIALS Ten newly diagnosed GBM patients were included in this study. All patients received standard radiation of 60 Gy in 30 fractions starting within 4–6 weeks after surgery with concurrent TMZ (daily, 75 mg/m2) and anlotinib (8mg per day, from day 1 to 14, every 3 weeks). After a 4-week break, adjuvant therapy including 6 cycles of TMZ (150–200 mg/m², from day 1 to 5, every 4 weeks) and 8 cycles of anlotinib (8mg per day, from day 1 to 14, every 3 weeks) was given. For patients completing adjuvant therapy, anlotinib alone (8mg per day, from day 1 to 14, every 3 weeks) was administrated until disease progression. RESULTS All patients completed concurrent chemo-radiotherapy without interruption. One patient developed grade 3 weight loss at 56th week and grade 3 presumed radiation-induced cognitive disturbance at 60th week. Fatigue and hypertension were frequently observed during treatment, which potentially be related to the treatment. No severe toxicity was observed in other patients. Up to this writing, none of these patients developed disease progression. CONCLUSION Anlotinib combined with the STUPP regimen is a potential choice for newly diagnosed GBM patients. It is well tolerated and the toxicity is manageable. It’s acceptable to continue enrolling of this Phase II study.

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