Study of three weekly nab-paclitaxel regimens in combination with carboplatin as first-line therapy in advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7659-7659 ◽  
Author(s):  
M. J. Hawkins ◽  
G. Manikhas ◽  
A. Makhson ◽  
S. Cheporov ◽  
S. Orlov ◽  
...  
Keyword(s):  
Large Scale ◽  
Response Rate ◽  
Performance Status ◽  
Sensory Neuropathy ◽  
Patient Characteristics ◽  
First Line ◽  
Serious Adverse Events ◽  
First Line Therapy ◽  
Grade 3 ◽  
Asco 2006

7659 Background: We previously reported that 130-nM albumin-bound form of paclitaxel (ABI-007, nab paclitaxel) 225 - 340 mg/m2 and carboplatin AUC of 6 mg/min·ml (C6), both administered on day (d) 1 every 3 weeks (q3w), produced an objective (PR/CR) response rate (ORR) of 27% in first line patients (pts) with NSCLC with median progression-free (PFS) and overall survivals of 6.0 and >10.3 months respectively [Hawkins et al., ASCO, 2006]. Grade 2 and 3 sensory neuropathy (SN) was 36–56%. The aim of the current study was to obtain clinical experience with weekly schedules of nab- paclitaxel in combination with C6 in NSCLC prior to initiating large scale clinical trials. Methods: 75 Pts with previously untreated, stage IIIB or IV NSCLC with measurable disease and a life expectancy of over 12 weeks were recruited into 3 cohorts (n = 25 each) of successive pts and received nab paclitaxel weekly using 3 different regimens (see table ). Results: Patient Characteristics: 75 pts (100% Caucasian; 84% male; median age, 60; performance status score: 0 [16%], 1 [84%]. Accrual was completed in each cohort and serious adverse events reviewed prior to accrual at the next dose level. The primary efficacy endpoints are provided in the table . Grade 3/4 hematologic toxicities were: neutropenia 32%/35%; thrombocytopenia, 19%/11%; anemia, 24%/3%. The most common non- hematologic toxicities (any grade) were fatigue, 48%; SN, 48%; nausea, 37%; alopecia, 40%; and vomiting, 26%. Grade 2 and 3 SN was 12–28%. Graded toxicity data by regimen will be presented. Conclusions: When combined with C6, the ORR was higher and there was less peripheral neuropathy for weekly nab-paclitaxel compared to our previous experience using q3w administration. [Table: see text] [Table: see text]

Dose escalation study of nab-paclitaxel followed by carboplatin as first line therapy in advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7132-7132 ◽  
Author(s):  
M. J. Hawkins ◽  
M. Georgy ◽  
A. Makhson ◽  
S. Cheporov ◽  
O. Sergey ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Performance Status ◽  
Area Under The Curve ◽  
Sensory Neuropathy ◽  
First Line ◽  
Serious Adverse Events ◽  
Dose Escalation Study ◽  
Efficacy Analysis ◽  
First Line Therapy ◽  
Primary Endpoints

7132 Background: Paclitaxel for injection formulated in Cremophor® and ethanol (Taxol®, Cremophor paclitaxel) 225 mg/m2 and carboplatin area under the curve of 6 mg/min·ml (C6) administered every 3 weeks (q3w) has produced an overall response rate (ORR) of 17% in first line patients (pts) with NSCLC with a 1-year survival of 34% [Schiller et al., NEJM, 2002;346:92]. The aim of this phase II study is to obtain clinical experience with a 130-nanometer albumin-bound form of paclitaxel (Abraxane®, ABI-007, nab™ paclitaxel) followed by C6 in NSCLC to determine a dose that approximates the toxicity of Cremophor paclitaxel/C6. Methods: Pts with previously untreated, stage IIIB or IV NSCLC with measurable disease and a life expectancy of over 12 weeks were recruited. In a dose escalation schedule, 4 cohorts (n = 25 each) of successive pts received nab paclitaxel at doses of 225, 260, 300, or 340 mg/m2 as 30-minute IV infusions followed by C6 q3w. The primary endpoints were the ORR (pts with an objective, confirmed complete or partial response) and toxicity. The primary efficacy analysis was based on all pts who received at least 1 dose of nab-paclitaxel and C6. Stable disease (SD) at ≥16 weeks was also assessed. Results: One hundred pts (100% white; 78% male; median age, 63; performance status score: 0 [11%], 1 [89%] were enrolled from 15 March–28 June of 2005. Accrual was completed in each cohort and serious adverse events reviewed prior to accrual at the next dose level. The results for ORR and SD at ≥16 weeks currently available are shown in the Table . The most common toxicities (any grade) were neutropenia, 43%; fatigue, 37%; sensory neuropathy, 37%; nausea, 35%; thrombocytopenia, 33%; anemia, 24%; alopecia, 24%; and vomiting, 21%. Conclusions: The combination demonstrated antitumor activity and was reasonably well tolerated. Mature data will be presented. [Table: see text] [Table: see text]

Mature data on capecitabine (X) + fractionated cisplatin (P) as first-line therapy in patients (pts) with advanced gastric carcinoma (AGC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4075-4075 ◽  
Author(s):  
M. Jin ◽  
L. Shen ◽  
B. Hu ◽  
J. Yu ◽  
Z. Wen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Response Rate ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
First Line ◽  
First Line Therapy ◽  
Highly Active ◽  
Advanced Gastric Carcinoma ◽  
Hand Foot Syndrome ◽  
Grade 3

4075 Background: Gastric cancer is one of the most common malignancies in Asia with an adjusted mortality rate above 20/100,000 population. 5-FU + fractionated P is a standard treatment for AGC in China. In a Korean study by Kim et al., X + P produced a response rate of 55% in pts with previously untreated AGC. Here we present mature efficacy/safety results in Chinese pts with AGC. Methods: 154 pts of a planned population of 120 pts were enrolled between Jun 2002 and Aug 2004. All had measurable AGC (WHO), Karnofsky performance status ≥60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy or adjuvant chemotherapy was permitted. Pts received × 1000 mg/m2 orally bid on days 1–14 + P 20mg/m2/day i.v. on days 1–5, every 3 weeks for 6 cycles. The primary endpoint was time to disease progression (TTP). Results: Baseline characteristics of the 141 evaluable pts (104 men, 37 women) are: median age 54 years (range 23–80), main sites of metastases: lymph nodes 45%, liver 40%, stomach 18%, skin 6%, other 6%, lung 5%, abdomen 4%. The overall response rate was 36%, including 13 complete responses and 38 partial responses. After a median follow-up period of 12 months, the median TTP is 9 months (95% CI, 9–12 months) and the median overall survival is 12 months (95% CI, 12–15 months). Median treatment duration was 6 cycles (range 3–6). The most common treatment-related clinical adverse events (all grades >5%) were: hand-foot syndrome (HFS) 25%, leucopenia 13%, and SGOT abnormality 12%. The most commongrade 3 adverse events were SGPT abnormality 3%, HFS 2%, and anemia 2%. There were no grade 4 adverse events. Most grade 3 adverse events improved or resolved after treatment or interruption except in 1 pt with anemia who withdrew after 2 cycles. Conclusions: X combined with fractionated P is highly active and very well tolerated as first-line treatment for AGC, with comparable results to 5-FU + P. No significant financial relationships to disclose.

Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel inHER2-Positive Metastatic Breast Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Grade 3

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.

Pemetrexed (MTA) and carboplatin (CBDCA) in the treatment of advanced pleural mesothelioma (MPM)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7093-7093 ◽  
Author(s):  
B. Castagneto ◽  
M. Mencoboni ◽  
D. Degiovanni ◽  
A. Muzio ◽  
L. Giaretto ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Entire Group ◽  
Hematologic Toxicity ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

7093 Background: Aim of this study was to evaluate the activity and toxicity of MTA and CBDCA combination as first line chemotherapy in advanced MPM. Methods: Chemonaive patients (pts) with histologically proven, an ECOG performance status (PS) 0–2, and measurable advanced MPM were considered. The schedule of administration was: pemetrexed 500 mg/m2 in combination with CBDA AUC 5, once every 21 days for 8 cycles. Results: From July 2003 to March 2005 76 pts (54 male and 22 female) have been treated with this combination chemotherapy. Median age was 62.7 years (range 40–70); median PS 0 (range 0–3); epithelial histologic findings were in 57 (75%), mixed in 13 (17.1%), sarcomatous in 3 (3.9%), and unspecified in 3 (3.9%) pts. A total of 537 cycles was administered (median 7, range 1 to 13). Grade 3 hematologic toxicity according to WHO criteria was seen in 43 (56.6%) pts (neutropenia in 30, thrombocytopenia in 8, and anemia in 5); grade 4 hematologic toxicity in 5 (6.6%) pts. The most common nonhematologic events were grade 3 nausea/vomiting in 10 (13.1%), and fever in 4 (5.3%) pts. 74 pts were evaluable for clinical response. There were 16 (21.%) partial responses (PR) and 3 (3.9%) complete responses (CR), for an overall response rate of 23.9%. 29 (38.2%) pts reported stable disease (SD). The overall survival was considered from date of diagnosis to date of death from any cause or to date of last follow-up. The median survival time for the entire group was estimated at 23 months. Conclusions: The results of this phase II study indicate that, at this dose and schedule, the combination of CBDCA and MTA is moderately active and that the profile of toxicity is acceptable in pts with advanced MPM. No significant financial relationships to disclose.

Prospective phase II trial of a combination of gemcitabine, cisplatin and UFT as first-line treatment in patients with advanced, unresectable, non-small cell lung carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18109-18109
Author(s):  
S. S. Jin ◽  
Y. Min ◽  
H. Kim ◽  
J. Ahn ◽  
Y. Jegal ◽  
...  
Keyword(s):  
Survival Time ◽  
Overall Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Performance Status ◽  
Small Cell ◽  
Time To Progression ◽  
Small Cell Lung ◽  
First Line ◽  
Grade 3

18109 Background: Most patients with advanced non-small cell lung cancer (NSCLC) receive either single agents or doublet chemotherapy. For non-elderly patients in good performance status, platinum-based double combinations represent the standard treatment. And oral UFT had the survival advantage in adjuvant setting. Therefore we performed a phase II study using the combination of gemcitabine, cisplatin and UFT as a first line therapy in patients with advanced NSCLC. Methods: Eligible patients had histologically or cytologically confirmed stage IIIB or IV NSCLC with good performance status and were chemotherapy-naive. This study was two-stage design and planned number of patients was forty-seven. Gemcitabine (1,250 mg/m2, 10 mg/kg/min on days 1 and 8) and cisplatin (75 mg/m2 on day 1) were injected intravenously and UFT (400 mg/day) was administered orally on day 1–14. Treatment repeated every 3 weeks. Primary end point was overall response rate and secondary end points were overall survival, time to progression and toxicity. Results: Thirty seven patients with advanced NSCLC were enrolled. The median age of the patients was 60 years (range: 44 to 72). The performance status (WHO) was 0 in 4, 1 in 30 and 2 in 3 patients. Twenty three patients completed six cycles. Complete response was achieved in 1 (3%) patient, partial response in 22 (59%) patients, stable disease in 9 (24%) patients. Overall response rate was 62% on intent to treat basis. Among patients who response evaluation was possible (33 patients), response rate was 70%. The median survival time was 14.5 months (95% CI 6.9, 22.3) and the 1 year survival was 35% and then median time to progression was 3.4 months(95% CI 3, 3.9). Toxicities were moderate and mostly hematological adverse events. Grade 3/4 neutropenia occurred in 37%, 5 patients with febrile neutropenia. Grade 3/4 anemia and thrombocypenia was occurred in 37% and 5%. Nonhematologic toxicities were mild. Conclusion: The combination therapy consisted of gemcitabine, cisplatin and UFT is active and well tolerable first line regimen for NSCLC patients. No significant financial relationships to disclose.

A phase II study of combination of bortezomib, liposomal doxorubin, and dexamethasone (VDD) as first line therapy for multiple myeloma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17504-17504 ◽  
Author(s):  
A. J. Jakubowiak ◽  
J. Friedman ◽  
T. Kendall ◽  
A. Al-Zoubi ◽  
M. S. Kaminski
Keyword(s):  
Peripheral Neuropathy ◽  
Partial Response ◽  
Phase Ii ◽  
Response Rate ◽  
Cell Transplant ◽  
First Line ◽  
Overall Response ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3

17504 Background: We have recently reported that a combination of bortezomib (Velcade), liposomal doxorubicin (Doxil), and dexamethasone (VDD) is very active and well tolerated in relapsed/refractory myeloma (MM) producing 83% overall response rate and 33% of complete (CR) or near complete (nCR) response rate. In the current study, we evaluated the activity of VDD as first line therapy in newly diagnosed patients with MM. The primary objective of this study was to determine the efficacy of this regimen. Methods: This is a phase II, single institution trial which opened in July 2005 with target accrual of 30 patients. EBMT criteria were used for evaluation of responses. The regimen was given as follows: Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11, Doxil at 30 mg/m2 on day 4, and Dexamethasone for a total of 160 mg per cycle, initially at 40 mg on days 1–4 and then 20 mg on days of Velcade and the day after. VDD was repeated every 3 weeks for a total of 6 cycles. Results: To date, 19 pts have been enrolled, 18 of whom are presently evaluable for response after receiving a mean of 4.7 cycles (range 1–6). The characteristics of the evaluable patients included the following: median age 58 (range 39–83), chromosome 13 deletion in 4 patients, beta2-microglobulin 4.4 (61% > 4.0). CR + nCR have been observed in 2 patients (11%), very good partial response (VGPR) in 5 patients (28%), partial response (PR) in 9 patients (50%) and minor response (MR) in 1 patients (5%) for an overall response (≥ MR) of 94%, ≥ PR of 89% and ≥ VGPR of 39%. All patients who proceeded to stem cell transplant collected without any problems. The regimen was very well tolerated. Most surprisingly, only 1 patient developed peripheral neuropathy grade 1. One patient developed pneumonia and PE and one patient grade 3 diarrhea, which was found to be secondary to cryptosporidium. Grade 3 or 4 neutropenia was observed in 6 patients and grade 3 thrombocytopenia in 1 patient. The most common grade 1 and 2 toxicities were thrombocytopenia and fatigue, both significantly less common than in relapsed patients treated with the same regimen. One patient developed grade 2 DVT and 1 grade 2 PPE. Conclusions: VDD combination shows high overall activity of 94% and ≥ 90% disease reduction of 39%. The regimen is very well tolerated and has a surprisingly low incidence of peripheral neuropathy. [Table: see text]

Multicenter phase II study of FOLFOX or biweekly XELOX and cetuximab as first-line treatment in patients with wild-type KRAS/BRAF metastatic colorectal cancer (mCRC) (FLEET study).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 463-463
Author(s):  
Ho Min Kim ◽  
Hitoshi Soda ◽  
Shoichi Hazama ◽  
Takao Takahashi ◽  
Naoki Nagata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Predictive Biomarker ◽  
Wild Type ◽  
First Line ◽  
First Line Therapy ◽  
Multicenter Phase ◽  
Grade 3 ◽  
Few Data

463 Background: Cetuximab and chemotherapy as first-line therapy for patients with KRAS wild type prolong survival. However, COIN trial has not demonstrated the survival benefit of FOLFOX or XELOX and cetuximab therapy. Few data are available on its benefit for patients with KRAS and BRAF wild-type. Methods: The aim of this study was to assess the efficacy of first-line FOLFOX or bi-weekly XELOX and bi-weekly cetuximab in KRAS/BRAF wt mCRC. Chemonaive patients received FOLFOX or biweekly XELOX (oxaliplatin 85 mg/ m2/day 1 plus capecitabine 2000/m2/days 1-7) and biweekly cetuximab 500mg m2/ day 1 every 2 weeks. Primary endpoint was response rate(RR), other secondary endpoints were PFS, OS, DCR, safety, DI and resection rate. KRAS test (codon12,13) and BRAF test (V600E) by direct sequence were performed in Yamaguchi University. Patients with KRAS/BRAF wt were enrolled in this study. The regimen of FOLFOX or XELOX were selected by investigator’s preference, not randomized. Results: From April 2010 to May 2011, 139 pts were preregistered. KRAS and BRAF were examined from paraffin-embedded sample. 70 (50.3%) pts were KRAS/BRAF wt, and 62 pts were enrolled: The main characteristics of the entered pts were: sex (M/F) 34/28, median age 66 yrs (range 34-83 yrs). Grade 3/4 adverse events were leucopenia 4.8%, neutropenia 25.8%, skin toxity (paronychia/fissure) 9.7%, and acne 9.7%. Two CR (3.2%) and 40 PR (64.5%), 15 SD (24.2%) and 3 PD (4.8%) 2NE were observed, with an overall response rate of 67.7% and a disease control rate (CR+PR+SD) of 91.9%. The RR of FOLFOX or XELOX were 64.9% (24/37) and 72.0% (18/25), DCR were 89.2% and 96% respectively. Conclusions: FLEET was the first multicenter phase II study with prospective KRAS/BRAF analysis as a predictive biomarker for cetuximab in first-line mCRC in Japan. Results of this study indicate that both biweekly combination regimens are feasible, tolerable, and clinically active. Biweekly XELOX+cetuximab study (FLEET2) is ongoing. Clinical trial information: UMIN000003253.

Multicenter Phase II Study of Irinotecan, Cisplatin, and Bevacizumab in Patients With Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

2006 ◽  
Vol 24 (33) ◽  
pp. 5201-5206 ◽  
Author(s):  
Manish A. Shah ◽  
Ramesh K. Ramanathan ◽  
David H. Ilson ◽  
Alissa Levnor ◽  
David D'Adamo ◽  
...  
Keyword(s):  
Response Rate ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Patient Characteristics ◽  
Time To Progression ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Upper Gastrointestinal Bleed ◽  
Grade 3

Purpose Bevacizumab improves survival in several solid tumor malignancies when combined with chemotherapy. We evaluated the efficacy and safety of the addition of bevacizumab to chemotherapy in the treatment of gastric and gastroesophageal junction (GEJ) adenocarcinoma. Patients and Methods Forty-seven patients with metastatic or unresectable gastric/GEJ adenocarcinoma were treated with bevacizumab 15 mg/kg on day 1, irinotecan 65 mg/m2, and cisplatin 30 mg/m2 on days 1 and 8, every 21 days. The primary end point was to demonstrate a 50% improvement in time to progression over historical values. Secondary end points included safety, response, and survival. Results Patient characteristics were as follows: median age 59 years (range, 25 to 75); Karnofsky performance status 90% (70% to 100%); male:female, 34:13; and gastric/GEJ, 24:23. With a median follow-up of 12.2 months, median time to progression was 8.3 months (95% CI, 5.5 to 9.9 months). In 34 patients with measurable disease, the overall response rate was 65% (95% CI, 46% to 80%). Median survival was 12.3 months (95% CI, 11.3 to 17.2 months). We observed no increase in chemotherapy related toxicity. Possible bevacizumab-related toxicity included a 28% incidence of grade 3 hypertension, two patients with a gastric perforation and one patient with a near perforation (6%), and one patient with a myocardial infarction (2%). Grade 3 to 4 thromboembolic events occurred in 25% of patients. Although the primary tumor was unresected in 40 patients, we observed only one patient with a significant upper gastrointestinal bleed. Conclusion Bevacizumab can be safely given with chemotherapy even with primary gastric and GEJ tumors in place. The response rate, time to disease progression (TTP), and overall survival are encouraging, with TTP improved over historical controls by 75%. Further development of bevacizumab in gastric and GEJ cancers is warranted.

Lenalidomide and Low Dose Dexamethasone As First Line Therapy for Newly Diagnosed Patients with Primary Plasma Cell Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 729-729 ◽  
Author(s):  
Pellegrino Musto ◽  
Vittorio Simeon ◽  
Giovanni D'Arena ◽  
Maria Carmen Martorelli ◽  
Maria Teresa Petrucci ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Low Dose ◽  
Response Rate ◽  
Plasma Cell Leukemia ◽  
Hematological Toxicity ◽  
Cell Leukemia ◽  
First Line ◽  
First Line Therapy ◽  
Primary Plasma Cell Leukemia ◽  
Grade 3

Abstract Abstract 729 Introduction: The prognosis of primary plasma cell leukemia (PPCL) remains poor. The “novel agents” have recently shown promising results in PPCL patients in case reports or small retrospective series. Here we describe the first prospective, multicenter, phase II clinical trial of PPCL, where lenalidomide in combination with low dose dexamethasone (Ld) was tested as initial therapy in newly diagnosed patients fulfilling the IMWG diagnostic criteria of PPCL. Patients and methods: Ld regimen consisted of lenalidomide 25 mg/d for 21 days and oral dexamethasone 40 mg on days 1, 8, 15, and 22 for each 28-day cycle. After 4 cycles, responding patients not eligible for stem cell transplantation (SCT) continued until 8 cycles of full-dose Ld, followed by a maintenance dose of single agent lenalidomide equal to 10 mg/d on days 1–21 of each 28-day cycle. Patients responding after 4 cycles and eligible for SCT proceeded according to the treatment centre's transplant policy. Patients not responding after 4 cycles or progressing during this treatment were considered off-study. Appropriate dose reductions (in particular for patients with reduced renal function at baseline), double contraception methods and anti-thrombotic/anti-infective prophylaxis were recommended. The primary end-point was early response rate according to IMWG uniform response criteria. Secondary end-points were PFS, OS, feasibility and efficacy of SCT, safety. Results: According to the Simon optimal two-stage adaptive design, twenty-three patients were enrolled in between March 2009 and May 2011. The male/female ratio was 1.1, and median age was 60 years (range 44–80). The median absolute number and percentage of circulating plasma cells were 4.280/μl (range 1.500–114.660) and 34% (range 21–90) respectively. Fifteen patients (65.2%) had abnormal renal function at presentation. Twenty-one patients (91.3%) were tested by FISH analysis and cytogenetic abnormalities were detected in all of them, del13q being the most frequently found (16 patients). Seventeen patients showed multiple chromosomal lesions. Involvement of chromosome 14 was observed in 18 patients, three of whom showed t(4;14). Chromosome 1q gain and del17p were detected in 10 and 7 patients, respectively. In the intention-to-treat (ITT) population, overall response rate (ORR) after at least one Ld cycle was 73.9% (17/23), with 8 patients (34.7%) achieving partial remission (PR), 5 (21.7%) very good PR (VGPR), 3 (13%) complete response (CR), and 1(4.3%) near CR (nCR) (VGPR or better: 39%). In the efficacy-evaluable (EE) population, 14 out of 15 patients who received the initially planned 4 Ld cycles (65.2% of the ITT population) responded (ORR 93.3%), achieving 5 PR (33.3%), 5 VGPR (33.3%), 1 near-CR (6.6%) and 3 CR (20%) (VGPR or better: 59.9%). The maintenance phase was reached and safely performed in 4 responding patients not eligible for SCT, 3 of whom relapsed after 2, 8 and 22 months, respectively. After Ld induction therapy, 8 patients received single (n. 4) or double (n. 4) autologous SCT (ASCT); another patient underwent a sequence of ASCT followed by non-myeloablative allogeneic SCT (AlloSCT). Six eligible patients did not receive ASCT frontline, due to initial Ld failure or adverse events; three of them underwent single ASCT (n. 2) or tandem ASCT/non-myeloablative AlloSCT (n. 1) after a bortezomib-based salvage therapy, achieving 2 CR and 1 PR. After a median follow-up of 23 months, median OS and PFS in ITT population were not reached and 22 months, respectively. All transplanted patients remained alive, although three of them relapsed and started salvage treatments; OS was 12 months in the 11 patients who did not receive ASCT (p < 0.001). The correspondent figures for PFS were 29 and 16 months, respectively (p < 0.01). Considering ITT population, multivariate analyses showed that SCT was positively correlated to both OS and PFS. There were 17 episodes of grade 3/4 non hematological toxicity, which occurred in 13 patients (5 infections, 3 renal, 3 metabolic, 2 gastro-intestinal, 2 skin, 1 fatigue, 1 thromboembolic), causing early interruption of Ld treatment in 4 patients. Grade 3/4 hematological toxicity (mainly neutropenia) occurred in 11 patients (47.8%). Conclusions: Ld may be a feasible and effective initial therapeutic option for PPCL, particularly in patients who receive ASCT after a short course of induction treatment. Disclosures: Musto: Celgene: Honoraria, Research Funding. Off Label Use: Lenalidomide as first line therapy of plasma cell leukemia. Petrucci:Celgene: Honoraria. Cascavilla:Celgene: Honoraria. Di Raimondo:Celgene: Honoraria. Caravita:Celgene: Honoraria. Morabito:Celgene: Honoraria. Offidani:Celgene: Honoraria. Bringhen:Celgene: Honoraria. Boccadoro:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Palumbo:Celgene: Consultancy, Honoraria.

Phase II study of infusional 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for metastatic colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4089-4089 ◽  
Author(s):  
S. Kopetz ◽  
K. Y. Glover ◽  
C. Eng ◽  
R. A. Wolff ◽  
D. Z. Chang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Intention To Treat ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
First Line Treatment

4089 Background: When compared to bolus 5-fluorouracil (F), leucovorin (L), and irinotecan (I) regimens such as IFL, the infusional F, L, I regimen (FOLFIRI) resulted in a improved toxicity profile with a response rate (RR) of 35% and median progression free survival (PFS) of 6.7 months. When combined with bevacizumab (B) as first-line treatment, IFL demonstrated improved activity with a RR of 45% and a median PFS of 10.6 months. Combining FOLFIRI and B may further improve the efficacy. Methods: We designed a single-arm, phase II trial of FOLFIRI+B with B (5mg/kg), I (180mg/m2), bolus of F (400mg/m2) and L (400mg/m2) with a 46-hour infusion of F (2400mg/m2) every 2 weeks. The primary endpoint was PFS. Chemotherapy naïve mCRC patients (pts) with a performance status of 0–2 received B alone on Day -14, starting FOLFIRI+B on Day 1. Proteomic and radiographic correlative studies were completed and will be reported separately. Results: N=41 pts, median age 56 y/o (range 26–78), M:F = 16:25, 5 pts with prior adjuvant therapy, were enrolled from 1/2005 to 1/2007. A total of 502 cycles have been administered (median = 12). The median PFS is 12.6 months. Response rate by intention-to-treat analysis was 62% (24 pts), with 33% stable disease (13 pts). Responses occurred after a median of 4 months of therapy. Fifteen pts remain on treatment; 26 pts are off study: 7 for progressive disease, 2 withdrew consent, 7 for toxicity and 2 for surgery unrelated to cancer. Eight pts were removed from the study for metastasectomies. Grade 3 or 4 toxicities included 17 occurrences of grade = 3 neutropenia, including 1 grade 4 febrile neutropenia, 4 grade 4 pulmonary emboli, 2 grade 3 hand-foot syndrome, and 1 grade 3 diarrhea. One pt included in the analysis developed a possible microperforation, manifested by peritonitis, after B alone and never received FOLFIRI. Conclusion: FOLFIRI+B is well-tolerated and efficacious, with an impressive PFS that compares favorably to historical controls. This regimen is an excellent choice as a first-line treatment for mCRC. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document