Phase II dose escalation study of sorafenib in patients with metastatic renal cell carcinoma (mRCC) who have had prior treatment with VEGFR-TKI antiangiogenic treatment

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16027-e16027
Author(s):  
A. P. Mancuso ◽  
E. Donato De Paola ◽  
A. Catalano ◽  
F. Calabrò ◽  
C. Messina ◽  
...  
Keyword(s):  
Standard Dose ◽  
Progression Free Survival ◽  
Median Number ◽  
Dose Escalation Study ◽  
Multikinase Inhibitor ◽  
Prior Therapy ◽  
Hand Foot Syndrome ◽  
Tki Treatment ◽  
Number Of Cycles ◽  
Metastatic Sites

e16027 Background: Sorafenib is an orally active multikinase inhibitor (Raf kinase, VEGFR 1, 2, 3 and PDGFR inhibitor) for the treatment of advanced RCC. The purpose of this study was to assess the efficacy and toxicity of Sorafenib in mRCC patients (pts) previously treated with an anti-angiogenic VEGFR-TKI using escalating dose levels. Methods: Pts with mRCC, PS 0–2 and adequate organ function were eligible. Pts received Sorafenib 400 mg/BID/continuously in 4-wk cycles. Pts with no progressive disease (evaluated at 12 weeks) continued to receive Sorafenib at the standard dose, while progressive pts received an increasing dose (600 mg BID) with early disease restaging after 4 weeks. Pts who progressed at 600 mg BID were taken off study. Efficacy was assessed by RECIST criteria. Results: 18 pts were entered; baseline characteristics: PS 0–1: 94%; median age 62 years (41–82); nephrectomy: 100%; surgery for metastatic disease: 28%, clear-cell 78%, papillary-cell 16%, sarcomatoid 6%.≥ 2 metastatic sites: 84%. 10 pts were refractory to cytokine treatment and all progressed or experienced unacceptable toxicity after anti-angiogenic VEGFR-TKI treatment, Sunitinib (13 pts) or Pazopanib (5 pts). Median number of cycles was 7.5 (1–16). Overall, 72% of pts had disease control without significant correlations between response to prior therapy and hypertension. 14 pts had progression free survival (PFS) of 4.3 months (mos). 4 pts are still in treatment with a median PFS > 8 mos. Of 6 pts in which the dose was escalated, 3 benefitted with a PFS of > 3 mos. The most common toxicity (NCIC 3.0, all pts) was grade (g) ≥ 1 diarrhea in 10 pts, g2–3 hand-foot syndrome in 7 pts and g-3 mucositis in 1 pt. Other hematological and non-hematological toxicities were g1 with a frequency < 15%. Conclusions: Sorafenib at doses of 400–600 mg/BID/continuosly results in acceptable and well tolerated salvage treatment after VEGFR-TKI failure. In progressive patients, treatment with a higher dose could be a valid option. Final and mature data will be presented in combination with translational research evaluating biological characteristics on tissue and blood. No significant financial relationships to disclose.

Phase II trial of ifosfamide in combination with sorafenib in patients with advanced soft tissue sarcoma: A Spanish Group for Research on Sarcomas (GEIS) study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10523-10523
Author(s):  
Xavier Garcia del Muro ◽  
Joan Maurel ◽  
Javier Martinez Trufero ◽  
Javier Lavernia ◽  
Antonio Lopez-Pousa ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Hepatic Function ◽  
Median Number ◽  
Hand Foot Syndrome ◽  
Number Of Cycles ◽  
Histologic Types ◽  
Ecog Ps

10523 Background: Recent studies suggest that VEGFR inhibition could play a role in the treatment of soft tissue sarcoma (STS). Prior studies by our group showed that the combination of ifosfamide with sorafenib resulted in preclinical additive activity and that was feasible and safe in the phase I trial. Methods: Patients (pts) with advanced STS, previously treated with doxorubicin, no prior ifosfamide, ECOG PS 0-2, and adequate hematological, renal and hepatic function, were enrolled in this multicenter phase II study, receiving sorafenib 400 mg bid po continuously and ifosfamide 2 g/m2 iv for 3 days together with mesna 400 mg/m2 every 3 weeks. The primary endpoint was progression-free rate (PFR) at 3 months. A one-sample binomial design was used (PFR P0=40%, P1=60%, α=0.10, β=0.20), requiring at least 19 of 35 pts free of progression at 3 months to be considered positive. Results: From September 09 to March 12, 35 pts were enrolled at 11 centers. Median age was 55 (18-73). PS: 0-13, 1-18; 2-4 pts. Histologic types were: LMS 12, Lipo 6, SS 5, MPNST 2, other 10 pts. . The median number of cycles administered per patient was 4. PFR at 3 months was 67%, with 23 pts being free of progression at 3 months. Median progression-free survival was 4.8 months (95% CI, 1.9-6.3) and median overall survival was 16.2 months. PR was achieved in 17% pts. Most common grade 3-4 toxicities were asthenia (25%), hand-foot syndrome (11%) and neutropenia (20%) resulting in 3 episodes of neutropenic fever. Other common toxicities (G1-4) included emesis (34%), rash (22%), diarrhea (34%), hypertension (11%) and mucositis (9%). Conclusions: The combination of ifosfamide and sorafenib is active and has acceptable toxicity in pts with doxorubicin pretreated STS. The PFR at 3 months might exceed the expected with ifosfamide alone warranting further investigation. Clinical trial information: EudraCT: 2007-002176-34.

Lenalidomide (Revlimid®) +/− Corticosteroids in Elderly Patients with Relapsed/Refractory Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3550-3550 ◽  
Author(s):  
Donna E. Reece ◽  
Esther Masih-Khan ◽  
Christine Chen ◽  
Lisa Wang ◽  
Saima Dean ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Creatinine Level ◽  
Single Agent ◽  
Age Groups ◽  
Progression Free Survival ◽  
Median Number ◽  
Time Points ◽  
Prior Therapy ◽  
History Of ◽  
Number Of Cycles

Abstract The combination of lenalidomide (Revlimid®) and dexamethasone (dex) is highly effective in multiple myeloma (MM) patients (pts) with relapsed/refractory disease. As MM is a disease of elderly individuals, we evaluated the outcome of pts 65 yrs and older who received Rev-based regimens through Celgene’s Expanded Access Program in Canada which commenced in 12/05; the results were compared with younger pts on this study. Our center has treated 69 pts who progressed after at least 1 prior regimen. Pts were required to have a minimum baseline neutrophil count of 1.0 x 109/L and platelet count of 30 x 109/L; serum creatinine level needed to be ≤220 umol/L unless a waiver was obtained. The median age was 60 yrs (35–79); 24 pts (35%) were 65 or older, 13 (19%) 70 or older and 4 (0.6%) 75 yrs or older. Fifty-two % were male; median baseline creatinine level was 91 umol/L (52–412); median β2-microglobulin was 214 nm/L (114–1420); Ig subtype was IgG in 42, IgA in 12, IgM in 1 and light chain only in 14. Prior therapy included ASCT in 59 pts (86%), thalidomide in 51 (74%), bortezomib in 21 (30%) and oral cyclophosphamide in 52 (75%); the median number of prior regimens was 2 (1–5). Rev was given with pulse dex in 44 pts (64%), prednisone in 7 (10%), dex and prednisone at different time points in 5 (7%) or as a single agent in 13 (19%); pts not receiving dex had a history of significant steroid toxicity. RESULTS: The older and younger pt groups were well-balanced with respect to baseline characteristics, with the exception that fewer older pts had undergone prior ASCT (54% vs. 80%; p=0.04). Rev + dex was given in 54% of the older pts, compared to 69% of the younger pts; 13% vs. 9% received Rev + prednisone, 4% vs. 9% received Rev + both dex and prednisone at different time points, and 29% vs. 13% received Rev alone in older and younger pts, respectively (p= 0.37). Median follow-up is 4 mos (0.5–8). To date, the median number of cycles of Rev +/− steroids was 4 (1–8) in both age groups. Among older pts, 46% remain on Rev +/− steroids; 54% have discontinued the trial due to disease progression (21%), toxicity (12.5%), pt withdrawal (12.5%) or death (8%). In the younger age group, 49% remain on Rev therapy, while 51% have stopped due to progression (31%), toxicity (4%), withdrawal (7%) or death (9%) (p= 0.62). Table 1 summarizes toxicity seen in the 2 age groups. Using standard EBMT criteria, the partial response rate was 58%, including 1 near CR, in the older pt group, compared with 56% in younger pts (p=0.15). The actuarial progression free survival (PFS) was 43% (95% CI 26–60%) and overall survival (OS) 74% (19–65%) in older pts, compared with 43% (26–60%) and 76% (52–87%), respectively, in younger individuals. CONCLUSION: The incidence of higher grade side-effects is not increased in older pts with relapsed/refractory MM treated with Rev +/− steroids; older MM pts achieve comparable response rates (approximately 60%); in this preliminary analysis, the PFS and OS in older vs. younger pts are identical. Table 1 Age N G 3–4 neutropenia G-CSF given Gr 3–4 thrombocytopenia Febrile neutropenia Any infection Gr 3–4 fatigue None of the differences were statistically significant. 65 or older 24 46% 54% 38% 12% 25% 13% Less than 65 45 44% 64% 24% 9% 16% 11%

First-line chemotherapy with irinotecan plus capecitabine for advanced colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14602-14602
Author(s):  
V. Michalaki ◽  
C. Gennatas ◽  
S. Gennatas ◽  
J. Vasiliou ◽  
V. Smyrniotis
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Adenocarcinoma ◽  
Progression Free Survival ◽  
Median Number ◽  
First Line ◽  
Free Survival ◽  
Gastrointestinal Side Effects ◽  
Number Of Cycles ◽  
Metastatic Sites ◽  
Line Chemotherapy

14602 Background: The effective, oral fluoropyrimidine capecitabine is increasingly replacing intravenous (IV) 5-FU/LV in colorectal cancer treatment. The aim of this study was to evaluate efficacy and safety of the combination chemotherapy with irinotecan plus capecitabine (XELIRI), in patients with advanced colorectal adenocarcinoma. Methods: Patients with advanced colorectal adenocarcinoma received a first-line chemotherapy with capecitabine (1000 mg/m2 twice daily) on days 1–14 and irinotecan (240 mg/m2) on day 1 of a 21-day cycle. Results: Twenty-eight patients were evaluable for response. Baseline characteristics: 18men, 10 women; median age 65.5 years (range, 49–73); colon cancer (71%), rectal cancer (29%). Most common metastatic sites were the liver (53.5%), lymph nodes (43%), lung (21%) and bones (18%). There were 7 partial responses (25%), 8 cases of stable disease (28.5%), and 13 cases of disease progression (46.5%). The median survival was 14 months (range, 2–28.8 months) and median progression-free survival was 7 months (range, 6- 26 months). The median number of cycles received was 7 (range, 3–15 cycles). Frequently encountered therapy-related events were leukopenia and gastrointestinal side effects including diarrhea. Conclusions: First-line capecitabine/ irinotecan is an active combination for the treatment of metastatic colorectal cancer achieving high efficacy with a good safety profile. No significant financial relationships to disclose.

Single-arm, phase 2 study of regorafenib plus nivolumab in patients with mismatch repair-proficient (pMMR)/microsatellite stable (MSS) colorectal cancer (CRC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3560-3560
Author(s):  
Marwan Fakih ◽  
Kanwal Pratap Singh Raghav ◽  
David Z. Chang ◽  
Johanna C. Bendell ◽  
Timothy Larson ◽  
...  
Keyword(s):  
Cytotoxic T Cells ◽  
Progression Free Survival ◽  
Maculopapular Rash ◽  
Median Number ◽  
North American Population ◽  
Immunomodulatory Activity ◽  
Multikinase Inhibitor ◽  
Primary Tumor Site ◽  
Combination Methods ◽  
Biomarker Analysis

3560 Background: The role of immunotherapy in the treatment of pMMR/MSS metastatic CRC is not established. A Japanese phase 1b trial in this setting showed the combination of regorafenib (multikinase inhibitor with immunomodulatory activity) plus nivolumab (anti PD-1) had encouraging activity and manageable safety (Fukuoka, 2020). This study further assessed the safety and efficacy of this combination. Methods: Patients (pts) from the US aged ≥18 years who progressed on/were intolerant to standard chemotherapy were enrolled. Regorafenib was given orally, once daily in 28-day (D) cycles (21D on/7D off) plus IV nivolumab 480 mg on D1. Regorafenib starting dose was 80 mg; if well tolerated, it could be escalated to 120 mg in Cycle 2. Primary endpoint was overall response rate (ORR; RECIST 1.1); secondary aims included disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and safety (NCI-CTCAE v5.0 grade). Biomarker analysis was exploratory. Results: 70 pts (59% male) started treatment. At baseline, median age was 57 years (range 34–85), ECOG PS 0/1 was 51%/49%, 67% had liver metastases (mets), and the primary tumor site was right-sided colon in 36% and rectum in 17%. Median number of cycles was 3.0 (range 1–13); 41% of pts escalated regorafenib to 120 mg. Five pts (7.1%) had a partial response (PR) lasting ≥16 weeks (wks) and 22 (31.4%) had stable disease (SD); pts without liver mets had a higher ORR (21.7%). In pts with tumor samples (n = 40), higher baseline expression (IHC) of cytotoxic T cells (CD3+/CD8+/GranzymeB+), Tregs (FoxP3+), and macrophages (CD68+) trended with clinical benefit (PR/SD ≥16 wks/PFS); pts with liver mets had lower expression. Lower plasma levels of biomarkers of vascular biology (e.g. VEGF-D, Ang-2, VWF) trended with longer PFS. Grade (Gr) 3 treatment-emergent adverse events (TEAEs) occurred in 53% of pts and Gr 4 in 10%. Three pts had a Gr 5 TEAE: n = 1 related to the combination (sepsis); n = 1 related to nivolumab only by investigator (sepsis); n = 1 unrelated to treatment (respiratory failure). Most common Gr 3/4 TEAEs: maculopapular rash (14%), fatigue (7%), pneumonia (6%), increased bilirubin (6%). Conclusions: Combination treatment with regorafenib (up to 120 mg/day) and nivolumab (480 mg every 28D) has manageable safety. Efficacy of this combination in the North American population did not emulate results in the Japanese population. Absence of liver mets and expression of specific biomarkers indicate a better response and may warrant further analysis. Clinical trial information: NCT04126733. [Table: see text]

Biweekly oxaliplatin plus capecitabine (OXXEL) versus oxaliplatin plus folinic acid-modulated 5-fluorouracil i.v. bolus (OXAFAFU) in metastatic colorectal carcinoma (MCC): Safety interim analysis of a Southern Italy Cooperative Oncology Group (SICOG) phase III trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3590-3590 ◽  
Author(s):  
C. Sandomenico ◽  
G. Filippelli ◽  
B. Massidda ◽  
A. Farris ◽  
D. Natale ◽  
...  
Keyword(s):  
Folinic Acid ◽  
Interim Analysis ◽  
Median Number ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Who Grade ◽  
Hand Foot Syndrome ◽  
Present Trial ◽  
Metastatic Sites ◽  
Oxxel Regimen

3590 Background: We have previously reported that OXAFAFU regimen significantly prolonged the overall survival of MCC patients (pts) in comparison with IRIFAFU regimen (Comella, Ann Oncol 2005). Moreover, the OXXEL regimen showed promising activity in phase II study (Comella, Cancer Chemother Pharmacol 2005). Comparison of these two regimens in terms of safety and activity is the aim of the present trial. Methods: Pts with MCC were randomly treated with: oxaliplatin 85 mg/m2 iv on day (D) 1, levo-folinic acid 250 mg/m2 plus 5-fluorouracil 850 mg/m2 bolus iv on D 2 (OXAFAFU); or oxaliplatin 100 mg/m2 iv on D 1, Xeloda 1,000 mg/m2 twice daily po from D 1 (evening) to D 11 (morning). Treatment was delivered every 2 weeks up to progression, or for a maximum of 12 cycles. Results: From May 2004 to December 2005, 191 eligible pts were recruited (OXAFAFU, 96 pts; OXXEL, 95 pts). Characteristics of pts were well balanced in OXAFAFU vs OXXEL arm: primary colon, 74% vs 72%; PS 0/1–2, 57/43% vs 65/35%; previous adjuvant CT, 24% vs 20%; liver metastases, 80% vs 83%; ≥ 2 metastatic sites, 54% vs 49%. At this interim analysis, with a median number of 8 (range, 1–12) cycles delivered in both arms, 143 pts (OXAFAFU, 73; OXXEL, 70) were assessed for safety. In OXAFAFU vs OXXEL arm, occurrence of WHO grade ≥ 3 toxicity was: neutropenia, 29% vs 3%; anemia, 2% vs 7%; thrombocytopenia 3% vs 7%; diarrhea, 4% vs 13%; vomiting, 4% vs 3%; hand-foot syndrome, 1% vs 7%. Conclusions: At this interim analysis, the OXXEL regimen appeared to produce significantly less neutropenia than the OXAFAFU regimen, at a price of an acceptable non-hematologic toxicity. Accrual will continue up to reaching the final sample size of 300 pts. No significant financial relationships to disclose.

A randomized, open label, prospective study comparing the association between sorafenib (So) and interleukin-2 (IL-2) versus So alone in advanced untreated renal cell cancer (RCC): Rosorc Trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5099-5099
Author(s):  
G. Procopio ◽  
E. Verzoni ◽  
S. Bracarda ◽  
S. Ricci ◽  
C. Sacco ◽  
...  
Keyword(s):  
Disease Control ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Antitumoral Activity ◽  
Open Label ◽  
Multikinase Inhibitor ◽  
Open Label Phase ◽  
Hand Foot Syndrome ◽  
Tumour Shrinkage

5099 Background: So is an orally active multikinase inhibitor with a well documented activity in advanced RCC. IL-2 is a pleiotropic cytokine with antitumoral activity depending on dose and schedule. The aim of the study is to evaluate the activity and the safety of So and IL-2 association compared to So alone. Methods: In this multicenter, randomized, open label, phase II study, 128 previously untreated metastatic RCC patients (pts) were randomized to receive 400 mg of So, orally given twice daily continuously, in combination with IL-2, 4.5 MIU administered subcutaneously, five times a week for six consecutive weeks any eight weeks (arm A), or So alone (arm B) at the same dose. Therapy continued until progression of disease or unacceptable toxicity. The primary end point was progression free survival (PFS) and the secondary endpoints were response rate, safety and overall survival. Eligible pts had histological diagnosis of RCC, ECOG 0–2, no brain metastases, measurable disease and any Motzer's score. Pts were stratified according to different histotypes and Motzer's score. Results: All pts were enrolled from October 2006 to February 2008. Response rates (all partial responses, PR) were 23 % and 10 % in arm A and B respectively. Overall disease control rates (PR + stable disease SD) were 81 % versus 74 %. Tumour shrinkage was reported in 52 % and 34 % of arm A and B therapies respectively. Median PFS was 38 weeks (range 6–104+) for So + IL-2 and 30 weeks (range 6–102+) for So alone. PFS at 1 year was 31% in the combination therapy versus 22% in arm B. The most common adverse events (AEs) were asthenia, hand foot syndrome, hypertension, fever, diarrhoea and mucositis. AE were usually low or moderate in severity and always reversible and manageable. Grade 3–4 AE were reported in 33% and 22% in arm A and B, respectively. Conclusions: The safety and efficacy data suggest that the association So + IL-2 is safe and feasible and, compared to So alone, improves tumour shrinkage, disease control rate and PFS. [Table: see text]

Role of trabectedin (T) in the management of advanced uterine leiomyosarcoma (U-LM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10530-10530
Author(s):  
F. Grosso ◽  
R. Sanfilippo ◽  
R. L. Jones ◽  
P. Collini ◽  
C. Morosi ◽  
...  
Keyword(s):  
Soft Tissue Sarcomas ◽  
Progression Free Survival ◽  
Median Number ◽  
Local Relapse ◽  
Tumor Control ◽  
Uterine Leiomyosarcoma ◽  
Systemic Treatments ◽  
Genetic Features ◽  
Metastatic Sites ◽  
Clinical Records

10530 Background: To explore the clinical impact of T in U-LM. T has been approved in Europe for second line treatment of advanced soft tissue sarcomas (STS). Efficacy is well established in liposarcoma and leiomyosarcoma. U-LMs display peculiar clinical and genetic features compared to other STS. These differences may be responsible for the sensitivity of this subtype to therapy, thus justifying an evaluation of the activity of T in a relatively homogeneous series of U-LM patients. Methods: From April 2000, 56 patients (pts) with advanced disease, previously exposed to a median of 3 chemotherapy lines (range 1–5), received T within an expanded access programme at two European referral institutions for sarcoma. The clinical records were reviewed focusing on response and treatment outcome. Two pts were excluded from the analysis having received only 1 course of T. Median age was 56 yrs (range 29–73), median number of metastatic sites was 2 (range 1–4), the most frequent metastatic site was lung (88%), 24 patients had a local relapse. Results: A total of 252 courses were delivered (median 3, IQR2–6) and 36% of patients received more than 5 courses of T. Fifty-two patients were evaluable for response. A partial response was observed in 11 patients and stable disease in 15, for a PR rate of 21% and a tumor control rate of 50%. The median progression-free survival was 3.6 months (CI95% 2.6–6.7), with 41% of patients free from progression at 6 months. Conclusions: These results compare favourably with other systemic treatments in advanced U-LMS and support their sensitivity to T. This should prompt further studies to prospectively evaluate the efficacy of T in U-LMS and elucidate possible biological predictive factors (e.g. DNA repair protein expression). [Table: see text]

Phase I dose escalation study of TG02 in patients with advanced hematologic malignancies.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6577-6577 ◽  
Author(s):  
Gail J. Roboz ◽  
Hanna Jean Khoury ◽  
Jamile M. Shammo ◽  
Mary Syto ◽  
Francis Burrows ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Escalation ◽  
Intensive Therapy ◽  
Study Drug ◽  
Underlying Disease ◽  
Median Number ◽  
Open Label ◽  
Dose Escalation Study ◽  
Multikinase Inhibitor ◽  
Dose Levels

6577 Background: TG02 is a novel multikinase inhibitor with a unique spectrum of activity, targeting both the cell cycle regulatory cyclin-dependent kinases (CDKs) 1 and 2 and the transcriptional regulators CDKs 7 and 9. TG02 also inhibits the emerging oncogenic MAPK ERK5 and the DNA damage response mediator CDK5. TG02 kills primary blasts from a variety of hematologic cancers and is curative in the MV4-11 model of FLT3-mutant AML. Methods: This is a first-in-man,single arm, open label, phase I dose escalation trial. The primary endpoints are dose-limiting toxicity (DLT), maximally tolerated dose (MTD ) and recommended phase 2 dose (RP2D). Patients (pts) ≥ 18 years with advanced hematological malignancies or newly diagnosed AML pts ≥ 65 years unfit for intensive therapy were enrolled onto daily (A) and intermittent (B, 5 days on 2 days off X 2 weeks) schedules. Pts had acceptable organ function and ECOG PS 1-2. Definition of DLT was G3-4 AST or ALT ≥7 days, G4 AST or ALT, G4 hyperbilirubinemia, any other NCI CTC G3-4 events not due to underlying disease. Dose levels on arm A were 10mg to 70mg and 15mg-150 mg on arm B. Results: Forty-five pts have received at least one dose of study drug. Median age was 66 years (range, 37-87) and 80% were ECOG 0-1. Disease types enrolled included: AML (80%), high-risk MDS (22%), and CML-BC (3%). The median number of previous regimens was 3 (range, 1-12). The MTD on arm A was defined at 50 mg daily based on 2 DLTs at the 70mg dose level (G4 hyperbilirubinemia, G4 fatigue). Enrollment to arm B has competed dose levels 15 (N=3), 30 (N=3), 50 (N=3), 70 (N=3), 100mg (N=3), and enrollment at 150mg is ongoing without DLT to date. Common drug related adverse events were nausea (42%), vomiting (23%), fatigue (18%), decreased appetite (15%), constipation and diarrhea (13% each). Preliminary PK demonstrated dose proportional increases in exposure and a T1/2 , supporting once daily dosing. Conclusions: The MTD for TG02 has been determined for the daily schedule at 50mg. Enrollment continues on the intermittent schedule. Schedules of every other day and week on/week off dosing will also be evaluated.

Neoadjuvant chemotherapy for locally advanced cervical cancer: Experience at the Instituto Oncologico Nacional SOLCA Guayaquil.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15571-e15571
Author(s):  
Guillermo Paulson ◽  
Katherine Garcia ◽  
Mayra Santacruz ◽  
Ruth Ginger Engracia ◽  
Jose Francisco Mendoza
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Invasive Cervical Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Number Of Cycles ◽  
Clinical Records ◽  
Cancer Experience

e15571 Background: Cervical cancer is the most common malignancy of women in Ecuador. The main problem of concomitant chemo-radiotherapy (CRT) is the delay in starting radiation therapy, economic and logistical problems for high demand in radiotherapy. It has been neoadjuvant chemotherapy (NACT) followed by CRT the main treatment at our center in order to find an alternative to long waits before the start of radiotherapy. The aim of this study was to determine the response to NACT followed by CRT in terms progression-free survival (PFS) and overall survival (OS). Methods: diagnosed with invasive cervical cancer locally advanced stage II-III were analyzed retrospectively reviewed clinical records of pre-existing data from 2008 to 2010. Results: after meeting the criteria of exclusion, leaving 116 cases. The median age: 49 years (range: 28-82 years). The histology was 73% (85) squamous cell carcinoma, 26% (30) adenocarcinoma and 0.9% (1) not specified. Patients with stage IIB: 81.9% (95), IIIA: 10.3% (12), IIIB: 7.8% (9). Of the 116 patients 69% (80) received NACT. The main NACT was paclitaxel 175mg/m2 + Cisplatin 75mg/m2 every 3 weeks 63.8% (74), the remaining group received another protocol, the median number of cycles of NACT was 5 (1 - 8 cycles), the start of radiotherapy since the conclusion of NACT was 53 days on average (1 to 285 days) and the main regimen of CRT concomitant was cisplatin 40mg/m2 weekly 47.5% (38). In the 49 patients who underwent NACT followed by CRT, a radiological study showed, complete response (CR) 38.8% (19), 18.4% partial response (PR) (9), disease progression (DP) 12.2% (6), stable disease (SD) 8.2% (4) and the end of treatment evaluation gynecological was performed and CR was obtained in 59.2% (29). Persistent or progressive disease after treatment was 22.4% (11), recurrence was 12.2% (6), local recurrence 2.0% (1), distant metastasis 10.2% (5). OS of NACT followed by CRT was 93.9% (46) and PFS was 65.3% (32), OS after CR was 96% (25 / 1) and then 91.7% PR (24 / 2) with p: 0.439. Conclusions: NACT followed by CRT is a valid option because it improves disease-related symptoms, but OS did not improve significantly even after CR.

mTOR inhibitor therapy for metastatic sarcomatoid clear cell renal cell carcinoma (ccRCC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 450-450 ◽  
Author(s):  
Diogo Assed Bastos ◽  
Martin Henner Voss ◽  
Christoph Karlo ◽  
Albulena Ajeti ◽  
Sujata Patil ◽  
...  
Keyword(s):  
Mtor Inhibitor ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Risk Groups ◽  
Median Number ◽  
Tumor Burden ◽  
Inhibitor Therapy ◽  
Cancer Center ◽  
Cell Renal Cell Carcinoma ◽  
Metastatic Sites

450 Background: Sarcomatoid variant describes a histomorphologic pattern with presence of spindle-cell features that can be seen across all subtypes of RCC. It is associated with an aggressive phenotype and poor prognosis. Outcome to mTOR inhibitor therapy was accessed in patients (pts) with ccRCC with sarcomatoid features. Methods: Patients with metastatic sarcomatoid ccRCC treated with mTOR inhibitors at our center were retrospectively identified. Demographic characteristics and treatment outcome were assessed. Overall response rate (ORR) was determined by formal response criteria (RECIST 1.1). Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: 29 pts were treated with temsirolimus (18) or everolimus (11). Median age was 57 years (53 to 61) and there were 21 male pts (72%). Median number of metastatic sites was 3 (1 to 7) and 18 pts (62%) had ≥ 3 metastatic sites. Distribution between Memorial Sloan-Kettering Cancer Center risk groups was 14% favorable, 72% intermediate, and 14% poor-risk disease. Median number of prior therapies was 1 (0 to 5) and 79% of pts received mTOR inhibitor as ≥ 2nd-line of therapy. Three patients (10.3%) achieved a partial response (PR), 11 (38%) stable disease (SD), and 15 (51.7%) had progressive disease (PD). Tumor shrinkage was observed in 9 pts (31%) and the mean change in tumor burden was +24% (-45% to +100%). Median PFS and OS were 3.4 months (CI: 1.4-5.3) and 8.3 months (CI: 4.8- 17), respectively. Conclusions: OS was poor in this heterogeneous group of pts. Future studies to characterize this variant at a molecular level are warranted and might identify predictive markers for clinical outcome in patients treated with mTOR inhibitors. [Table: see text]

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