Triplet chemotherapy (TC) with FOLFIRINOX regimen in metastatic colorectal cancer (mCRC): Experience of two French centres.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 776-776 ◽  
Author(s):  
Emmanuelle Samalin ◽  
Christelle De La Fouchardiere ◽  
Simon Thézenas ◽  
Matthieu Sarabi ◽  
Eric Assenat ◽  
...  
Keyword(s):  
Response Rate ◽  
Primary Tumour ◽  
Objective Response ◽  
Tumour Response ◽  
Complete Response ◽  
Median Number ◽  
R0 Resection ◽  
Secondary Resection ◽  
Grade 3 ◽  
The Impact

776 Background: TC is a treatment option for mCRC to improve the tumour response rate in selected patients (pts) and the conversion rate of initially nonresectable liver metastases. The aim of this study was to evaluate the impact and feasibility of FOLFIRINOX regimen in mCRC pts. Methods: We selected all mCRC pts from the ICM and CLB French centres with unresectable disease treated from October 2000 to May 2012 with FOLFIRINOX alone or combined with bevacizumab or cetuximab. Clinical data were collected in a mCRC-specific data base and analysed. Results: 159 pts (52% of men), median age 58 yrs (range: 24-76) were treated with FOLFIRINOX (D1 oxaliplatin 85 mg/m² IV over 2H, then irinotecan 180 mg/m² IV over 90 min and elvorin 200 mg/m², then 5-fluorouracile 200 mg/m² and 2,400 mg/m² IV over 46H, D1=D15) alone (68%) or combined with cetuximab (24%) or bevacizumab (8%) as first–line treatment (88%). Primary tumour was located in colon (77%) or rectum (23%), and 134 pts (84%) presented with synchronous metastases: liver (96%), lung (46%), peritoneum (11%) and nodes (20%). Median number of courses was 8 (range: 1-26). There was 1 toxic death. Grade 3-4 toxicities were as follows: diarrhoea (23%), neuropathy (24%), cutaneous (9%), neutropenia (21%), febrile neutropenia (1%), thrombopenia (4%). Objective response rate according to RECIST V1.0 was 72% [95% CI: 65-79] including 12 pts with complete response. The primary tumour was resected in 127 pts (79%) and 19% had KRAS mutated tumour. Among the 105 pts (66%) with initially non-resectable liver-limited disease (LLD), 59 pts (56%) were eligible for secondary resection and a R0 resection rate was achieved for 44 pts. Median overall survival was 49 months [95% CI: 37-62] and 72 months [95% CI: 48-84] in resected LLD population. Conclusions: These results confirm the feasibility of FOLFIRINOX regimen with or without targeted therapies and its efficacy in LLD selected mCRC population.

Triplet chemotherapy (TC) with FOLFIRINOX regimen in metastatic colorectal cancer (mCRC): Experience of the Val d’Aurelle Center.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3633-3633
Author(s):  
Emmanuelle Samalin ◽  
Virginie Loriot ◽  
Simon Thézenas ◽  
Eric Assenat ◽  
Fabienne Portales ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Metastases ◽  
Targeted Therapies ◽  
Primary Tumor ◽  
Response Rate ◽  
Objective Response ◽  
Complete Response ◽  
Median Number ◽  
Grade 3 ◽  
The Impact

3633 Background: TC is a treatment option for mCRC to improve the tumor response rate in selected patients (pts) and the conversion rate of initially non-resectable liver metastases. The aim of this study was to evaluate the impact and feasibility of FOLFIRINOX regimen in mCRC pts. Methods: All mCRC pts with non-resectable disease who have received FOLFIRINOX alone or combined with targeted therapies (bevacizumab or cetuximab) from October 2000 to December 2010 were selected for this analysis. Clinical data were collected in a mCRC specific data base and analyzed by the end of 2011. Results: Ninety two pts (52% of men), median age 59 yrs (range: 27-76) were treated with FOLFIRINOX (D1 oxaliplatin 85 mg/m² IV 2H then irinotecan 180 mg/m² IV 90 min and elvorin 200 mg/m², then 5FU 200 mg/m² and 2400 mg/m² by 46H infusion, D1=D15) alone (64%) or combined with cetuximab(30%) or bevacizumab (6%), as 1st-line in 82 pts (89%). Prophyllactic G-CSF was given in 58% of them. Primary tumor was located in colon (58%) or rectum (42%), and 64 (69%) of pts presented with synchronous metastases: liver 100%, lung 40%, peritoneum 17% and nodes 17%. Median number of cures was 8 (range: 1-12). There was 1 toxic death. Grade 3-4 toxicities were: diarrhea 22%, neuropathy 21%, cutaneous 12%, neutropenia 28%, febrile neutropenia 0%, thrombopenia 6%. Objective Response rate according to RECIST criteria was 72% [CI95% 61-81] including 10 pts with complete response (11%). The primary tumor was resected in 70 pts (76%) and 14% had KRAS mutated tumor. Among the pts with liver metastases, 63 (68%) pts were evaluated for secondary resectability by a multidisciplinary committee and 40 pts (43%) had resection achieved (70% R0). Median overall survival was 49 months [CI95%28-62]. Conclusions: These results confirm the feasibility of FOLFIRINOX regimen with or without targeted therapies and its efficacy in terms of response rate and overall survival as 1rst-line treatment in selected mCRC pts.

Phase II Results of Bendamustine in Combination with Rituximab in Relapsed Indolent and Mantle-Cell Non-Hodgkin’s Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2710-2710 ◽  
Author(s):  
Richard H. Van der Jagt ◽  
Philip Cohen ◽  
Bruce D. Cheson ◽  
Anil Tulpule ◽  
Jordan A. Herst ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Prior Chemotherapy ◽  
Non Hodgkin's Lymphoma ◽  
Mantle Cell ◽  
Grade 3

Abstract Objective: The objective of this study was to evaluate the efficacy and safety of bendamustine HCl (TREANDA®) in combination with rituximab in patients with relapsed non-Hodgkin’s lymphoma (NHL). Background: Bendamustine is a novel hybrid, alkylating agent with single-agent activity in multiple hematologic and solid tumors. It induces cell death via both apoptosis and the apoptosis-independent pathway of mitotic catastrophe. The combination of bendamustine and rituximab has been shown to exhibit a synergistic antitumor effect on NHL cells. Methods: This Phase II, multicenter study enrolled adult patients with relapsed, indolent B-cell or mantle-cell NHL who were not refractory to rituximab (defined as progression ≤6 months of last rituximab dose). Patients received rituximab 375 mg/m2 intravenously (IV) on day 1 and bendamustine 90 mg/m2 IV on days 2 and 3 of a 28-day cycle for 4 to 6 cycles. An additional dose of rituximab 375 mg/m2 IV was given 1 week before the first cycle of bendamustine and 4 weeks after the last cycle. Results: The intent-to-treat (ITT) population included 66 patients (59% men) with a median age of 60 years (range, 40–84). Indolent histologic phenotype was seen in 54 patients with the following histologic subtypes: follicular center cell (61%), small lymphocytic (15%), lymphoplasmacytic (3%), and marginal zone (3%); 18% had mantle-cell lymphoma (MCL). A total of 85% of patients had stage III/IV disease. These patients relapsed from a median of 1 prior chemotherapy (range: 0–5), with 56% having had prior treatment with rituximab. Patients with no prior chemotherapy relapsed following biologic therapy. In the ITT population, the overall objective response rate (ORR) was 94% (complete response [CR]/complete response unconfirmed [CRu], 41%; partial response [PR], 53%); 6% had stable disease. The ORR for the 12 MCL patients was 92% (CR/CRu, 42%; PR 50%). For all patients, the median duration of response and progression-free survival has not been reached after a median follow-up of 8.3 months (range, 0.14–31 months). Grade 3/4 neutropenia was seen in 41% of patients (7%, febrile neutropenia). Common nonhematologic toxicities (grade 1/2, grade 3, grade 4) were nausea (68%, 0%, 0%) and fatigue (53%, 5%, 0%); one patient had grade 3 sepsis. No alopecia was observed. Conclusions: Bendamustine administered in combination with rituximab produced a high objective response rate and was generally well tolerated in patients with relapsed indolent and mantle-cell NHL who were not refractory to rituximab. These results suggest that the combination of bendamustine and rituximab may be comparable in activity to R-CHOP, and further studies of this combination are warranted.

Phase I-II Trial of Oral Cyclophosphamide, Prednisone and Lenalidomide (Revlimid®) (CPR) for the Treatment of Patients with Relapsed and Refractory Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3055-3055
Author(s):  
Donna E. Reece ◽  
Esther Masih-Khan ◽  
Arooj Khan ◽  
Saima Dean ◽  
Sharon Fung ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dose Level ◽  
Research Funding ◽  
Response Rate ◽  
Objective Response ◽  
Median Number ◽  
Prior Therapy ◽  
Best Response ◽  
Level 3 ◽  
Grade 3

Abstract Abstract 3055 Lenalidomide (Revlimid®) and dexamethasone is an effective regimen for relapsed/refractory (rel/ref) multiple myeloma (MM) patients (pts) with an overall response rate of 60% and median time to progression of 13.4 months (Dimopoulos ME, et al. Leukemia 2009; 23: 2147-52). We combined lenalidomide with the alkylating agent combination of cyclophosphamide and prednisone—an older regimen with minimal cumulative myelosuppression and good activity as second or third line therapy (Trieu Y, et al, Mayo Clin Proc 2005; 80: 1582). The CPR regimen consisted of cyclophosphamide (CY) on days 1, 8, and 15, lenalidomide on days 1–21 and prednisone 100 mg q 2 days in a 28-day cycle. ASA 81 mg/day was given as DVT prophylaxis. Three dose levels were evaluated using a 3 × 3 dose escalation design. Thirty-two pts were entered between 11/2007-06/2009; median age was 64 (42-80) yrs, 60% were male, and immunoglobulin isotype was IgG in 19 (62%), IgA in 8 (25%) and light chain in 4 (13%) pts. Median β2-microglobulin level was 257 (92-767) nm/L, albumin 39 (34-48) g/L, creatinine 83 (50-126) μmol/L, platelet count 355 (75-479) × 109/L and ANC 2.5 (1.1-6.1) × 109/L. The median number of prior regimens was 2 (1-5). Prior therapy included: ASCT (single in 91%; double in 19%), thalidomide (28%) and bortezomib (50%). FISH cytogenetics were available in 13 pts; 1 had del 13q but none had t(4;14) or del p53. Table 1 summarizes protocol treatment delivered. Table 1. Dose level N Cyclophosphamide dose (mg/m2) Lenalidomide dose (mg) Prednisone dose (mg) Median # cycles given 1 3 150 15 100 12 (12–34+) 2 3 150 25 100 10 (9–23) 3 26 300 25 100 17 (5–28+) 1–3 (All) 32 150–300 15–25 100 19 (5–34+) Dose limiting toxicity was not observed during cycle 1 at any dose level. Grade 3–4 toxicities during the trial included: thrombocytopenia in 7 (22%) and neutropenia in 9 (29%), managed with dose reduction and/or growth factors; five episodes of febrile neutropenia occurred, all at dose level 3. In cohort 3, other grade 3–4 non-hematologic toxicities included 1 episode each of abdominal pain/bacteremia, hypokalemia, fatigue, sick sinus syndrome, cardiac amyloidosis, perforated diverticulum and 2 episodes of DVT. Two heavily pretreated pts developed 2° MDS, including 1 previously treated for lymphoma, 43 and 190 mos after the diagnosis of MM. The best response using modified EBMT criteria was documented at a median of 7 (1-26) cycles and included the following: dose level 1 (1 CR, 2 PR); dose level 2 (1 VGPR, 2 PR); dose level 3 (4 CR, 14 VGPR, 11 PR, 1 MR and 1 stable disease). At a median F/U of 16 (5-34) months, 13 pts remain on study and 18 have progressed at a median of 10 (2-23) mos; 1 was lost to F/U and 9 have died of progressive MM. The 1-year actuarial OS and PFS rates are 93% (95% CI 76–98%) and 78% (95% CI 60–89%), respectively. We conclude: 1) the combination of full doses of the agents in CPR can be given in a 28 day cycle with an acceptable safety profile; 2) the objective response rate (CR + PR + MR) in all 32 pts to date is 94%; 3) the 1-year OS of 93% and PFS of 78% compare favorably with other 3-drug combinations in rel/ref MM pts; 4) further evaluation of this regimen in newly diagnosed pts would be of interest. Disclosures: Reece: Celgene: Honoraria, Research Funding. Off Label Use: Combination of lenalidomide and cyclophosphamide and prednisone in relapsed and refractory myeloma patients. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria.

Efficacy and safety of nivolumab (NIVO) plus ipilimumab (IPI) in patients with melanoma (MEL) metastatic to the brain: Results of the phase II study CheckMate 204.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9507-9507 ◽  
Author(s):  
Hussein Abdul-Hassan Tawbi ◽  
Peter A. J. Forsyth ◽  
Alain Patrick Algazi ◽  
Omid Hamid ◽  
F. Stephen Hodi ◽  
...  
Keyword(s):  
Objective Response ◽  
Complete Response ◽  
Median Number ◽  
Disease Assessment ◽  
Response Data ◽  
Grade 3 ◽  
Favorable Safety ◽  
The Brain ◽  
Clinical Trial Information

9507 Background: Brain metastases (BMts) are a major cause of morbidity/death in MEL. We report the first efficacy data in MEL patients (pts) with BMts who received NIVO+IPI in study CheckMate 204. Methods: In this multicenter US trial (NCT02320058), MEL pts with ≥1 measurable BMt 0.5-3.0 cm and no neurologic symptoms or steroid Rx received NIVO 1 mg/kg + IPI 3 mg/kg Q3W x 4, then NIVO 3 mg/kg Q2W until progression or toxicity. Pts with severe adverse events (AEs) during NIVO+IPI could receive NIVO when toxicity resolved; stereotactic radiotherapy (SRT) was allowed for brain oligo-progression if an assessable BMt remained. The primary endpoint was intracranial (IC) clinical benefit rate (complete response [CR] + partial response [PR] + stable disease [SD] > 6 months). The planned 90-pt accrual is complete; we report efficacy and updated safety for 75 pts with disease assessment before the Nov 2016 database lock. Results: Median age was 59 yrs (range 22–79). Median number of induction doses was 3; 26 pts (35%) received 4 NIVO+IPI doses and 38 pts (51%) began NIVO maintenance. Response data are reported at a median follow-up of 6.3 months (Table). The IC objective response rate (ORR) was 56% (95% CI: 44–68); 19% of pts had a complete response. IC and extracranial responses were largely concordant. Rx-related grade 3/4 AEs occurred in 48% of pts, 8% neurologic, including headache and syncope. Only 3 pts (4%) stopped Rx for Rx-related neurologic AEs. One pt died of immune-related myocarditis. Conclusions: In CheckMate 204, prospectively designed to investigate NIVO+IPI in MEL pts with BMts, NIVO+IPI had high IC antitumor activity with objective responses in 56% of pts, CR in 19%, and no unexpected neurologic safety signals. The favorable safety and high anti-melanoma activity of NIVO+IPI may represent a new Rx paradigm for pts with asymptomatic MEL BMts and could change practice to avoid or delay whole brain RT or SRT. Clinical trial information: NCT02320058. [Table: see text]

Phase II Trial of Irinotecan in Children With Relapsed or Refractory Rhabdomyosarcoma: A Joint Study of the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group

2007 ◽  
Vol 25 (4) ◽  
pp. 356-361 ◽  
Author(s):  
Gilles Vassal ◽  
Dominique Couanet ◽  
Elizabeth Stockdale ◽  
Anne Geoffray ◽  
Birgit Geoerger ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Median Number ◽  
Tumor Burden ◽  
French Society ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Multiagent Chemotherapy

PurposeThis phase II study was designed to evaluate the efficacy of irinotecan administered intravenously once every 3 weeks in pediatric patients with recurrent or refractory rhabdomyosarcoma.Patients and MethodsA total of 35 patients younger than age 20 years, with refractory or relapsed rhabdomyosarcoma for which standard treatments have failed, received irinotecan at 600 mg/m2administered as a 60-minute infusion every 3 weeks. Concomitant treatments included atropine for cholinergic symptoms, loperamide for diarrhea at the first liquid stool, and preventive antiemetic treatment. Tumor response was assessed every two cycles until progression according to WHO criteria.ResultsThe best overall response rate to irinotecan was 11.4% (95% CI, 3.2 to 26.7%; 2.9% complete responses, 8.5% partial responses) from all patients recruited. The median times to progression and survival were 1.4 and 5.8 months, respectively. A total of 112 cycles were administered, with a median number of two cycles per patient (range, 1 to 16). The most common grade 3/4 toxicities were neutropenia (46%), abdominal pain or cramping (17%), cholinergic syndrome (14%), nausea/vomiting (11%), anemia (11%), thrombocytopenia (9%), and diarrhea (6%).ConclusionIn heavily pretreated children with a high tumor burden who have been treated with multiagent chemotherapy, irinotecan administered intravenously as a single agent, at 600 mg/m2every 3 weeks, showed an interesting objective response rate and a good tolerance profile in rhabdomyosarcoma.

Vincristine, irinotecan, and temozolomide in patients with relapsed and refractory neuroblastoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e22009-e22009
Author(s):  
Jia Zhu ◽  
Zijun Zhen ◽  
Juan Wang ◽  
Tingting Chen ◽  
Suying Lu ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Wild Type ◽  
Salvage Regimen ◽  
Brain Involvement ◽  
Grade 3 ◽  
Metastatic Sites ◽  
Grade Iii

e22009 Background: The combination of irinotecan, temozolomide and vincristine has been proposed as an effective salvage regimen for some pediatric malignancies. Thus, we sought to evaluate this combination for patients with relapsed or refractory neuroblastoma (NB). Methods: Forty-six patients with relapsed or refractory NB were treated with the combination of vincristine (1.5 mg/m2 i.v. day 1), irinotecan (50 mg/m2 /day i.v. days 1–5) and temozolomide (100 mg/m2 /day p.o. days 1–5) (VIT) during the period 2011–2019. All toxicities were documented. Results: A total of 251 cycles (median 6 cycles/patient) were administered. A complete response (CR) was achieved in 5 patients, partial response (PR) in 27 patients, stable disease (SD) in 8 patients, and progression disease (PD) in 6 patients, with an overall objective response rate (CR+PR) of 69.6%. Eighteen patients developed diarrhea with Grade III or less. Grade 1-2 hematologic toxicity occurred in 10 patients. Grade 3-4 hematologic toxicity developed in 32 patients. VIT was an effective regimen for different metastatic sites. Overall objective response rates to VIT combination for patients with mediastinum, bone marrow/bone, lymph node, abdomen and brain involvement were 100.0%, 80.0%, 77.8%, 50.0%, 42.9%, respectively. UGT1A*28 genotyping performed in 7 patients revealed wild type. Diarrhea occurred in 4 of them. Conclusions: The shorter, 5-day VIT regimen is an active and well-tolerated salvage regimen in relapse/refractory NB.[Table: see text]

Gemcitabin (G) plus cisplatin (P) versus etoposid (E) plus cisplatin in advanced/metastatic non-small cell lung cancer (NSCLC): Preliminary results of a randomized monocentric study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18155-18155
Author(s):  
A. Bousahba ◽  
F. Bereksi-Reguig
Keyword(s):  
Treatment Response ◽  
Response Rate ◽  
Objective Response ◽  
Survival Rates ◽  
Complete Response ◽  
Stage Iiib ◽  
Grade 3 ◽  
Intent To Treat ◽  
Metastatic Sites ◽  
Ecog Ps

18155 Background: we performed a randomized monocentric study to compare the treatment response of two chemotherapy doublets EP versus GP. Survival rates and toxicity are the secondary endpoints. Methods: from December 2003 to October 2006, patients with non-operable stage IIIB /IV histological or cytological proven NSCLC, ECOG PS = 2, were randomized to: (A) gemcitabin 1250 mg/m2 on d 1, 8 plus cisplatin 80 mg/m2 on d1 q3w for 6 cycles or (B) cisplatin at same dose followed by etoposid 100 mg / m2 on d1, 2, 3 q3w. The sample size was estimated at 64 patients per treatment arm to provide a power of 0.80 to detect a 20% difference in response rate between the two groups at the 5% level. Results: one hundred thirteen chemonaïve patients were enrolled (A: 57, B: 56), median age 61 years (arm A) and 57.5 years (arm B), stage IIIB (42.1% A vs 41.1% B), two or more metastatic sites (34% A, 39% B), PS 1 (68.4% A, 69.6% B). 360 cycles were administered 187 (A) and 173 (B) with a median of 3 cycles per patient in each group. Two patients were excluded from analysis. One hundred one patients were evaluable for toxicity, 90 for response. 47 pts were evaluable in A and 43 pts in B with treatment response in intent to treat principle respectively: complete response (1.8% - 0%), partial responses (29.1% and 20.7%). The objective response rate was 30.9% (95% CI 18.8%-43.2%) in A, 20.7% (95% CI 9.8%-31.6%) in B, no change (36.4% and 37.7%) and progressive disease (18.2% and 22.6%). Median duration of objective response 8.2 months (A) and 8.3 months (B), median time to progression : 8.0 months (A) and 7.5 months (B). Incidences of grade 3–4 toxicities were respectively in arms A and B: nausea-vomiting (37%-12.5%), leucopenia (5.6%-14.6%), neutropenia (13%-37.5%), thrombopenia (0–2.1%), anemia (13%-6.3%). Febril neutropenia occurred in 1.9% (A) and 8.3% (B). One toxic death occurred in arm B. Conclusions: preliminary analysis indicates that GP had a more favourable toxicity profile and a higher activity is suggested for the GP regimen. The enrolment is continued. No significant financial relationships to disclose.

Feasibility of hypomethylating therapy in patients with renal insufficiency

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7089-7089
Author(s):  
G. Batty ◽  
H. Kantarjian ◽  
J. J. Issa ◽  
G. Garcia-Manero ◽  
S. Pierce ◽  
...  
Keyword(s):  
Renal Insufficiency ◽  
Myeloid Leukemia ◽  
Histone Deacetylase Inhibitors ◽  
Response Rate ◽  
Objective Response ◽  
Standard Of Care ◽  
Complete Response ◽  
Median Number ◽  
Epigenetic Therapy ◽  
Myelomonocytic Leukemia

7089 Background: Epigenetic therapy with hypomethylating agents (HA) is the standard of care in patients (pts) with myelodysplastic syndrome (MDS). Although neither 5-azacytidine (5AZA) nor 2'-deoxy azacytidine (decitabine; DAC) are excreted by the kidneys, many studies exclude pts with a serum creatinine level (sCr) ≥ 1.5 mg/dL. Moreover, there are no reports of use of these agents in pts with renal insufficiency (RI) commonly seen in pts with MDS. Methods: We investigated the outcomes of pts with RI and MDS, chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML) receiving therapy with HA. RI was defined by a sCr ≥ 1.5 mg/dL. We examined the compliance, dose adjustments (DA), and complications of treatment with DAC and 5AZA given at standard doses. We used the International Working Group criteria to evaluate the response rates. Data for pts with sCr > 2 mg/dL were compared to pts with sCr ≤ 2 mg/dL (Kantarjian H, et al, Blood. 2007). Results: Forty-two pts with sCr ≥ 1.5 mg/dL (including 17 with MDS, 16 with AML, and 9 with CMML) were treated with DAC or 5AZA alone or in combination with other agents (primarily histone deacetylase inhibitors). 14 (33%) and 28 (67%) of the pts received 5AZA and DAC, respectively. The median number of courses was 4.5 (range 1–19). 9 pts (21%) required treatment delay or discontinuation, and 12 pts (28%) required dose reduction (DR). Overall, 25 (62%) had an objective response (OR), and 4 pts (9%) had complete response (CR). 15 (36%) and 7 (17%) of the pts experienced episodes of therapy-related infections and bleeding, respectively. Among 12 pts who had sCr > 2.0 mg/dL, 7 pts (58%) required DR due to myelosuppression (n = 3) and to worsening of renal function (n = 4). The incidence of complications, DA, and the response rate were not significantly different for pts with sCr > 2.0 mg/dL. Conclusions: The use of HA is well tolerated in pts with MDS and AML and RI who achieved comparable OR rates to those without RI. Dose adjustment might be required in some pts. [Table: see text] [Table: see text]

Phase II trial of nemorubicin hydrocloride (nemorubicin) in combination with cisplatin (cDDP) in patients (pts) with hepatocellular carcinoma (HCC): First step results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4593-4593
Author(s):  
F. Izzo ◽  
A. M. Catino ◽  
T. J. Vogl ◽  
M. Middleton ◽  
J. W. Valle ◽  
...  
Keyword(s):  
Tumour Response ◽  
Hepatic Arterial Infusion ◽  
Complete Response ◽  
Median Number ◽  
Dna Intercalator ◽  
Minor Response ◽  
Biochemical Alterations ◽  
Vein Thrombosis ◽  
Disease Stabilization ◽  
Grade 3

4593 Background: Nemorubicin is a novel DNA-intercalator, mainly metabolized in liver by CYP3A4 enzyme and showing synergic antitumor activity with cDDP. The objective of this study was to evaluate the efficacy and adverse effects of nemorubicin administered by intra-hepatic artery in combination with cDDP to unresectable HCC pts. Methods: The study was in two HCC pt populations: intermediate risk (IRP) (CLIP 0–1, bilirubin < 1.5 x upper normal limit, no portal vein thrombosis [PVT]) and advanced risk (ARP) (CLIP 2, bilirubin < 2.5 mg/dL, PVT admitted). Treatment was repeated every 4–6 weeks for a maximum of six courses, if no toxicity and disease progression occurred. A single-arm, Simon's minimax two-stage design was adopted to evaluate the primary endpoint of tumour response (WHO criteria). In the first step >5/18 responses (IRP) and >2/10 responses (ARP) are needed to proceed with the second step. Results: Twenty-three IRP pts (13 evaluable) and 13 ARP pts (10 evaluable) were enrolled. The median number of treatments was 3 (range 1–6) in IRP (dose 600 mcg/m2 nemorubicin and 60 mg/m2 cDDP) and 4 (range 1–4) in ARP (dose 400 mcg/m2 nemorubicin and 60 mg/m2 cDDP). In IRP, so far 1 pt (8%) achieved complete response, 3 pts (23%) had partial response (PR), 5 pts (38%) had minor response (MR)/disease stabilization (SD) >3 months. In ARP, 2 pts (20%) had PR, satisfying the first step efficacy criteria. Also, 2 ARP pts (20%) had MR/SD. Overall, the main grade 3 and 4 hematological toxicities were thrombocytopenia (47%), leukopenia (42%), anemia (12%) and neutropenia (6%). Grade 3 and 4 biochemical alterations were aspartate aminotranferase (29%) alanine transferase (24%) and bilirubin increase (12%). The most frequent adverse events were fatigue (35%), vomiting (29%), diarrhoea (24%) and nausea (18%). Conclusions: Hepatic arterial infusion of nemorubicin with cisplatin showed promising activity in the first step of the study and it was a well tolerated regimen. These encouraging results warrant further development in HCC pts. No significant financial relationships to disclose.

Randomized phase II trial of maintenance sunitinib versus placebo following response to chemotherapy (CT) for patients (pts) with advanced urothelial carcinoma (UC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 265-265 ◽  
Author(s):  
Petros Grivas ◽  
David M. Nanus ◽  
Walter Michael Stadler ◽  
Stephanie Daignault ◽  
Robert Dreicer ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Placebo Response ◽  
Complete Response ◽  
Median Number ◽  
Progression Rate ◽  
Open Label ◽  
Best Response ◽  
Response To Chemotherapy ◽  
Ecog Ps

265 Background: UC response to CT is not durable. Angiogenesis may play a role in the progression of UC. We evaluated whether maintenance sunitinib delays progression after response to CT. Methods: Pts with ECOG PS 0-2, adequate organ function, stable disease, partial or complete response (SD, PR, CR) after 4-6 cycles of CT for advanced UC were randomized to oral sunitinib 50 mg/day, 28 days on, 14 days off (6-week cycle) or placebo. Disease was assessed every 12 wks. At progression, placebo pts were offered open label sunitinib. Primary endpoint: progression rate at 6 months (ms); secondary endpoints: safety, objective response rate, survival, VEGF/sVEGFR2 serum level changes. Using a randomized selection design 42 pts/arm has 90% probability of selecting sunitinib if true reduction in 6-ms progression rate is 15% (from 50% to 35%). Results: Study was closed early due to slow accrual. 54 pts with median age 69 years, median ECOG PS 1, 70% with bladder primary, 26 with SD, 23 with PR, 5 with CR to CT were randomized to sunitinib (26) or placebo (28). The median number of cycles was 2/arm (sunitinib 0-15, placebo 0-13). The 6-ms progression rate was 81% (95%CI 61-93%), median time-to-progression (TTP) 5 ms (0.3-22.2, 95%CI 2.4-6.3) for sunitinib and 75% (95%CI 55-89%), 2.7 ms (0.8-19.6, 95%CI 2.5-7.4) for placebo. Response rate in pts with SD at enrollment was 9% for sunitinib and 7% for placebo. Most common G3/4 AEs on sunitinib were diarrhea (15.4%/0%), fatigue (15.4%/3.8%), thrombocytopenia (15.4%/7.7%), hypertension (11.5%/0%). 16 placebo pts received sunitinib with best response 1 PR (6.25%), 6 SD (37.5%), 5 PD (31.25%); 4 not response evaluable. Median TTP was 3.4 ms (0.1-22, 95%CI 1.6-5.5). 11 pts had G3/4 AEs, 5 pts discontinued sunitinib due to AEs (4 related, 1 unrelated). Placebo pts had no change in VEGF/sVEGFR2 over time. Sunitinib pts had no change in VEGF but sVEGFR2 significantly decreased after 1 cycle (p<0.0001) and at progression (p=0.0002). VEGF/sVEGFR2 did not correlate with TTP. Conclusions: Maintenance sunitinib was feasible but did not improve 6-ms progression rate; open label sunitinib had limited activity. sVEGFR-2 decreased on sunitinib.

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