First-line cisplatin (P) with docetaxel (TXT) or vinorelbine (VNR) in patients with advanced non-small cell lung cancer: A randomized phase II trial of the Gruppo Oncologico Italia Meridionale

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19042-e19042
Author(s):  
V. Gebbia ◽  
D. Galetta ◽  
V. Lorusso ◽  
M. Caruso ◽  
F. Riccardi ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Hematological Toxicity ◽  
First Line ◽  
Primary Endpoints ◽  
Randomized Phase Ii ◽  
P 75 ◽  
Ecog Ps

e19042 Background: P-based doublets are considered standard therapy for advanced NSCLC. The GOIM consider P/VNR as a reference treatment. P/TXT doublet has been reported to be active but it's not well known its real impact on QoL in comparison to P/VNR. Methods: Pts received either 6 courses of P/TXT or P/VNR with QoL and safety being the primary endpoints. Secondary endpoint included response rate, TTP, OS, and tolerability. Patients with stage IV/IIIB, age ≤70, and ECOG PS 0–1, were eligible. Sample size was calculated according to Fleming's single-stage procedure. QoL was analysed using the EORTC questionnaire, responses and toxicity according to the RECIST and NCI-CTC criteria. Pts were randomized to: TXT 75 mg/m2 over 60 min followed by P 75 mg/m2 on d1 every 21 d, or VNR 30 mg/m2 on d 1,8 and P 80 mg/m2 on d1 every 21 d. Results: From 12/06 to 3/08 86 pts were enrolled: P/TXT 42pts, M/F 32/10, IIIB/IV 8/34, squamous/not-squamous:13/29, median age 61 (r 41–70); P/VNR 44 pts, M/F 35/9, IIIB/IV 10/33, squamous/not-squamous 14/30, median age 62 (r 44/70). No statistically significant differences were observed in QoL among the two arms. Detailed analysis of side-effects showed no difference among the two regimens with the exception of G3–4 neutropenia and leukopenia with were slightly higher in the P/VNR arm (p=0.02 and p=0.0005 respectively). The use of G- CSF/darbopoietin was more frequent in pts treated with P/VNR than in the P/TXT arm (p=0019). Conclusions: Final data show an equivalence among the two arms regarding QoL and activity but with a slightly more hematological toxicity in the P/VNR arm. Both regimens are to be considered as standards in the treated of advanced NSCLC. [Table: see text]

Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis

2019 ◽  
Vol 26 (6) ◽  
pp. 1331-1342
Author(s):  
Irena Ilic ◽  
Sandra Sipetic ◽  
Jovan Grujicic ◽  
Milena Ilic
Keyword(s):  
Overall Survival ◽  
Objective Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival

Introduction Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. Material and methods A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. Results The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79–0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69–1.01), p = 0.06 and OR = 1.46 (95% CI 0.90–2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16–66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23–3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28–1.87, p < 0.00001). Conclusions The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.

A randomized phase II trial comparing pulsed erlotinib before or after carboplatin and paclitaxel in patients with stage IIIB or IV non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7619-7619 ◽  
Author(s):  
G. J. Riely ◽  
C. M. Rudin ◽  
M. G. Kris ◽  
E. Senturk ◽  
C. G. Azzoli ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Stage Iiib ◽  
Preclinical Models ◽  
Phase 3 ◽  
Randomized Phase Ii ◽  
Pulsatile Administration ◽  
Common Grade ◽  
Grade 3

7619 Background: A randomized phase 3 trial failed to show any improvement in response rate (RR) or overall survival (OS) when erlotinib was added to carboplatin and paclitaxel (TRIBUTE). However, preclinical data suggested that administration of erlotinib before or after chemotherapy may improve efficacy of chemotherapy [Gumerlock et al ASCO 2003, Solit et al Clin Can Res 2005]. We designed this trial to test the hypothesis that administration of pulsed erlotinib prior to or following chemotherapy would improve the response rate in patients with advanced NSCLC. Methods: All patients had chemotherapy naive, stage IIIB or IV NSCLC and were former or current smokers. All patients received carboplatin (AUC 6) and paclitaxel (200 mg/m2). Patients were randomly assigned to one of three arms: erlotinib 150 mg days 1,2, and chemotherapy on day 3; erlotinib 1500 mg days 1, 2 and chemotherapy on day 3; or chemotherapy on day 1 and erlotinib 1500 mg on days 2,3. Patients received up to six 21-day cycles of treatment. The primary endpoint was overall RR (CR+PR) using RECIST. We planned to enroll 29 patients to each arm in a “pick the winner” design comparing arms to the chemotherapy alone arm of TRIBUTE (RR 19%) with a desirable RR of 50%. Results: Eighty-seven patients were randomized to 3 arms. Accrual is complete. The most common grade 3/4 toxicities were neutropenia (39%), fatigue (15%), and anemia (12%). Grade 3/4 rash or diarrhea were uncommon. Conclusions: Treatment with erlotinib before (150 mg on days 1 and 2 or 1500 mg on days 1 and 2) or after (1500 mg on days 2 and 3) administration of carboplatin and paclitaxel failed to improve response rates compared to TRIBUTE. The benefit of pulsatile administration of erlotinib predicted by preclinical models was not evident in this clinical trial. Supported by Genentech, Inc. [Table: see text] [Table: see text]

Recurrent/metastatic salivary gland malignancies (RMSGM): Final report of 60 cases treated with cisplatin plus vinorelbine (DDP+VNB).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5548-5548
Author(s):  
Fulvia Pedani ◽  
Mario Airoldi ◽  
Massimiliano Garzaro ◽  
Luca Raimondo ◽  
Simona Carnio ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Phase Ii Trial ◽  
Final Report ◽  
Moderate Activity ◽  
Second Line ◽  
First Line ◽  
Adenoid Cystic ◽  
Randomized Phase Ii ◽  
Ecog Ps

5548 Background: RMSGM are not amenable to the usual treatment with surgery and post-operative radiotherapy. The role of chemotherapy (CT) for RMSGM is palliative only. VNB showed moderate activity in our experience (Bull Cancer 85:892;1998) and in a randomized phase II trial we had demonstrated that the DDP+VNB combination had a better outcome than VNB alone (Cancer 91:541; 2001). In this abstract we report the final results of this combination in 60 cases. Methods: From April 2001 to February 2009 , 60 cases with RMSGM were enrolled. All patients received the following regimen: DDP 80 mg/sm d.1 + VNB 25 mg/sm d. 1,8 every 3 weeks. The study foresees a maximum of 6 cycles. Results: Patients characteristics were as follows: 35 males (58%) and 25 females (42%).; median age: 56 yrs (range 20-68); median ECOG PS: 1 (0-2); histology: adenocarcinoma 15 (25%), adenoid cystic ca. 34 (57%), others 11 (18%); site of disease: local 30 (50%) , mts +/- local 30 (50%). Forty-two pts received DDP+VNB as first line CT (70%) while 18 pts (30%) had the combination as second-line CT (30%). After a median of 5 cycles of first line DDP+VNB responses were: 3 CR (7%), 10 PR (24%), 14 NC (33%) and 15 PD (36%). After a median of 4 cycles of second line CT responses were: 0 CR; 1 PR (5%), 6 NC (33%) 11 PD (62%). Median survival: 10 months (3-29) for first line CT ; 4 months (1-12) for second line CT. G3-4 toxicity: neutropenia (20%), anemia (12%), nausea/vomiting (12%) , peripheral toxicity (3%). Conclusions: DDP+VNB is an effective first line CT in RMSGM ; second line CT has a low palliative activity. Toxicity seems acceptable. This regimen could be suitable for an integration with new biologic target agents.

Correlation of single nucleotide polymorphisms in NER pathway genes with toxicity in advanced non-small cell lung cancer patients treated with chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18115-e18115
Author(s):  
Ling Zhang
Keyword(s):  
Advanced Nsclc ◽  
Venous Blood ◽  
Stage Iv ◽  
Hematological Toxicity ◽  
Nucleotide Polymorphisms ◽  
Lung Cancer Patients ◽  
New Therapeutic Approaches ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps ◽  
Predictive Effect

e18115 Background: New therapeutic approaches are being developed based on the findings that several genetic abnormalities underlying NSCLC could influence chemosensitivity. We assessed whether polymorphisms in genes of NER pathway, such as ERCC5, ERCC6, MMS19L, CCNH, XPC, RRM1, can affect the tolerability of platinum-based chemotherapy in advanced NSCLC pts. Methods: Eligible pts had histological or cytological confirmed stage IV or IIIB (with malignant pleural effusion) chemo-naïve NSCLC, ECOG PS of 0 to 2 and adequate organ function. Pts received vinorelbine 25 mg/m2 or gemcitabine 1000 mg/m2 on day 1 and 8, or docetaxel 75 mg/m2 or taxel 175 mg/m2 on day 1 plus cisplatin 75 mg/m2 or carboplatin AUC=5 on day 1, every 21 days per cycle, for a maximum of six cycles, unless disease progression or unacceptable toxicity occurred. Hematology and biochemistry analyses were repeated every cycle or before chemotherapy for d8 treatment. Toxicity was classified according to CTC AE 3.0. Venous blood was collected and genomic DNA was isolated. Polymorphisms were assessed. SNPs in ERCC6 (A/G 1413, A/G 1213 and A/G 1097), XPC (T/C 500 and A/C 940), ERCC5 (G/C 1104), RRM1 (−37C/A), CCNH (T/C 270) and MMS19L (G811A) were assessed. Results: Totally 388 pts were included prospectively from Oct 2005 to Mar 2009. Median age was 61 years; 68.8% were male, 36.2% were ECOG PS 1, 33.2% had stage IIIB. The median follow-up time was 18 months (range 8–66 months). Hematological toxicity was the most common AE. SNPs of MMS19L and ERCC6 can predict the AE of chemotherapy in NSCLC,leucopenia (P=0.020), jaundice (P=0.039) by MMS19L. In terms of grade 3-4 AE, SNPs of MMS19L and RRM1 -37C/A have much more predictive effect. SNPs of MMS19L were good at total AE (P=0.042), thrombopenia (P=0.035), SNPs of RRM1 -37C/A were for vomiting (P=0.046) and jaundice (P=0.014). Conclusions: Polymorphisms in ERCC6, MMS19L, RRM1, can predict the tolerability of platinum-based chemotherapy in advanced NSCLC patients. Polymorphisms in other genes of NER pathway, such as ERCC5, CCNH, XPC, have no predictive effect.

POF (paclitaxel plus FOLFOX) versus IP PAC (intraperitoneal paclitaxel plus FOLFOX) versus FOLFOX as a first-line treatment in advanced gastric cancer (AGC): Update from a multicenter, randomized phase II trial, FNF-004 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4035-4035
Author(s):  
Rongbo Lin ◽  
Yigui Chen ◽  
Jinfeng Zhu ◽  
Peicheng Lin ◽  
Wujin Chen ◽  
...  
Keyword(s):  
Peritoneal Cavity ◽  
Peritoneal Metastasis ◽  
Response Rate ◽  
Phase Ii Trial ◽  
First Line ◽  
Primary Tumor Site ◽  
Randomized Phase Ii ◽  
Line Setting ◽  
Clinical Trial Information ◽  
Better Than

4035 Background: The PFS with POF was statistically significantly improved and IP PAC was trending to improve compared to FOLFOX in first-line setting in AGC were reported in 2019 ASCO-GI (abstract 6). Update and subgroup analysis were released herein. Methods: The patients with AGC were randomized to three groups. The POF or IP PAC was paclitaxel 135 mg/m2intravenously (POF) or paclitaxel 80 mg/m2 intraperitoneally (IP PAC) followed by mFOLFOX6 omitted 5-Fu bolus. Every 14 days repeated for all three regimens. Up to 9 cycles of treatment were administered, followed by S-1 until disease progression. The primary endpoint was PFS. Results: Between Nov 2015 and May 2018, 89 pts (30 POF, 29 IP PAC, 30 FOLFOX) were randomly allocated. PFS, OS and RR were seen in the table below. Either POF or IP PAC was statistically significantly better than FOLFOX in PFS. In subgroup with female, peritoneal metastasis, ascites, lymphadenopathy in peritoneal cavity, number of organs involved > 2, POF was statistically significantly better than FOLFOX in PFS. In subgroup with female, gastrium of primary tumor site, peritoneal metastasis, ascites, no lymphadenopathy out of peritoneal cavity, IP PAC was statistically significantly better than FOLFOX in PFS. Intravenously docetaxel plus S-1 still saw response after IP PAC. Conclusions: either POF or IP PAC improved survival compared to FOLFOX, especially in patients with female or peritoneum metastasis. Only POF, not IP PAC, improved response rate compared to FOLFOX. Clinical trial information: NCT02845908. [Table: see text]

FOLFOX versus POF (paclitaxel plus FOLFOX) versus IP PAC (intraperitoneal paclitaxel plus FOLFOX) as a first-line treatment in advanced gastric cancer (AGC): A multicenter, randomized phase II trial, FNF-004 trial.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 6-6
Author(s):  
Rongbo Lin ◽  
Hui Li ◽  
Yigui Chen ◽  
Jinfeng Zhu ◽  
Peicheng Lin ◽  
...  
Keyword(s):  
Response Rate ◽  
Phase Ii Trial ◽  
Abdominal Cavity ◽  
Local Concentration ◽  
First Line ◽  
Randomized Phase Ii ◽  
Significant Difference ◽  
Grade 3 ◽  
Clinical Trial Information ◽  
First Line Treatment

6 Background: Double regimens are commonly accepted for AGC in East Asia. However, triple regimens are recommended in west countries. POF regimen (reported in 2007, 2008, 2009, 2010 ASCO) appeared to be of good efficacy and was well tolerated in patients with AGC. Intraperitoneal paclitaxel showed high local concentration in abdominal cavity and low systemic toxicity. The aims of this study were to find out if the POF and IP PAC was more effective with manageable side effects than FOLFOX in AGC (reported in 2017 ASCO-GI for feasibility analysis). Methods: The patients with AGC were randomized to three groups. The POF consisted of a 3-hour infusion of paclitaxel 135 mg/m2, followed by FOLFOX omitted 5-Fu bolus. The IP PAC consisted of paclitaxel 80 mg/m2 intraperitoneally plus FOLFOX. Every 14 days repeated for all three regimens. Up to 9 cycles of treatment were administered, followed by S-1 until disease progression. The primary endpoint was PFS. Results: Between Nov 2015 and May 2018, 89 pts (30 POF, 29 IP PAC, 30 FOLFOX) were randomly allocated. PFS, OS and RR were seen in the table below. POF was better in PFS and RR than FOLFOX, although no statistically significant difference in RR. IP PAC was trend to be better in PFS than FOLFOX, but not in RR. OS was unmatured. The most common adverse events of grade 3 or 4 were neutropenia and neuropathy, but no significant difference among three groups. Conclusions: Both POF and IP PAC improved survival compared to FOLFOX. Only POF, not IP PAC, improved response rate compared to FOLFOX. Clinical trial information: NCT02845908. [Table: see text]

Randomized phase II trial of two sequential schedules of docetaxel (D) and cisplatin (C) followed by gemcitabine (G) in patients with advanced non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18154-18154
Author(s):  
E. Galligioni ◽  
V. Gebbia ◽  
G. Cartenì ◽  
T. Gamucci ◽  
F. Grossi ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Stage Iiib ◽  
Ethic Committee Approval ◽  
First Line ◽  
Randomized Phase Ii ◽  
Local Ethic Committee Approval ◽  
Grade 3

18154 Background: C based doublets remain the cornerstone for first line treatment of advanced NSCLC but the role of sequential use of chemotherapy is still investigational. Aim of this study was to assess the activity and toxicity of 3 courses of C and D followed by 3 courses of single agent G, to reduce C exposure and sequentially administer 2 second generation cytotoxic drugs. The weekly D/C schedule was further investigated, to reduce toxicity. Methods: Chemotherapy naive stage IIIB or IV measurable NSCLC pts, aged 18–70 and PS 0–1, were stratified by stage (IIIB vs IV) and randomized, after local ethic committee approval and signed informed consent, to D and C (both 75 mg/m2 on day 1) q21 days for 3 cycles (Arm A), or to D and C (both 25 mg/m2 on days 1, 8, 15) q28 days for 3 (Arm B). Responding or stable pts of each arm, were treated with 3 additional cycles of G (1,200 mg/m2 on days 1, 8) q 21 days. Primary endpoint of the study was response rate (RECIST). Sample size was calculated of 42 pts per arm, considering worthy of further investigation a regimen with =14 objective responses. Results: Between May 2005 and October 2006, 88 pts were enrolled (Arm A/B: 43/45), with 69 evaluable so far (median age 63 yrs, median PS 0, and M/F ratio 53/16). Toxicity (NCI-CTG criteria) after 3 cycles, evaluable on 67 (32/35) pts, was mainly hematological, with grade 3/4 neutropenia in 17 pts (17/0), neutropenic fever in 1 (arm A), infections in 2 (arm B), grade 3/4 thrombocytopenia in 3 (1/2) and grade 3/4 anemia in 2 (arm A). Non-hematological grade 3/4 toxicity consisted of fatigue (4/1), diarrhea (4/1), pulmonary toxicity (1/4), pain (2/3), stomatitis (1/2) and alopecia (2/0). Fifty one pts (A/B: 29/22) are evaluable for response after 3 cycles, with 16 PR (55%) and 7NC in arm A and 1CR+6PR (32%) and 7NC in arm B. Objective responses after 6 cycles, available only in few pts so far, show 1CR+10PR in arm A and 2PR in arm B. At a median FU of 6.5 months, 60/85 pts are alive (33/27) and 25 are dead (8/17), with 3 pts, never treated, lost to f. up. Conclusions: From these preliminary results, CD combination appears active and manageable while the activity of G, cannot be defined yet. Data collection is continuing and analysis will be completed and mature, by the time of the meeting. [Table: see text]

Gemcitabine (G) and cisplatin (C) as first-line treatment of metastatic breast cancer (MBC): Results of phase II trial.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 273-273
Author(s):  
M. Karthaus ◽  
I. Poddubnaya ◽  
L. Churilova ◽  
R. Khasanov ◽  
T. Veremeychuk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Metastatic Breast ◽  
Hematological Toxicity ◽  
Line Treatment ◽  
Toxicity Profile ◽  
First Line ◽  
First Line Treatment

273 Background: G has been studied in combination with a variety of agents known to be active in cancer. G has a mild toxicity profile. GC is active in various advanced tumors. Splitting of C dose (D 1 + d8) is better tolerated and can be a good alternative to once a cycle in pts with advanced breast cancer. This phase II trial evaluates G (1000 mg/m2) C (35 mg/ m2) d1+8 repeated every 21 d in the 1st-line treatment of metastatic breast cancer (MBC). The primary objective of the study was to determine the objective tumor response rate (ORR) of 1st-line GC in patients with metastatic breast cancer.The one-stage design tested the null hypothesis that the true response rate for this population should be equal to 50% for efficacy. Overall survival (OS), time to progression (TTP) and toxicity were evaluated. Methods: 70 female MBC pts with the median age of 49.8 ys (range 29.6-80.0) were enrolled. Tumor assessment was performed every other cycle by standard criteria including CT or MRI. 67 pts received a total of 310 cycles GC, out of these 54 pts were evaluable for efficacy. Results: Complete and partial responses were observed in 7/54 (13.0%) and 19/54 (35.2%) evaluable pts, respectively with an overall response of 48.2%. Disease stabilization was noticed in 19/54 (35.2%) pts. Progression was observed in 5/54 (9.3%) pts. TTP was 33.9 weeks (95% CI, 23.9-48.0). OS was 84.0 weeks (95% CI, 58.6-119.3). 1-year overall survival rate was 68.4% (95% CI, 53.6-79.3%). Hematological toxicity G4 was neutropenia in 14.9% (10/67), and no G4 thrombocytopenia. Hypotension G4 (1.5%) was the only severe non-hematological toxicity. Conclusions: GC in the first-line treatment of MBC, demonstrated a substantial overall response rate and had a good toxicity profile. GC is a suitable option for first-line MBC in selected pts.

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