A nomogram predicting survival of patients (pts) with metastatic or unresectable urothelial cancer (UC) treated with cisplatin-based chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5055-5055 ◽  
Author(s):  
D. F. Bajorin ◽  
I. Ostrovnaya ◽  
A. Iasonos ◽  
M. I. Milowsky ◽  
M. Boyle ◽  
...  
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Cox Model ◽  
Performance Status ◽  
Phase Iii ◽  
Poor Performance Status ◽  
Long Term Outcome ◽  
Phase Ii Studies ◽  
Phase Iii Trials ◽  
Pre Treatment

5055 Background: Cisplatin-based chemotherapy is the standard of care for pts with metastatic or unresectable UC with phase III studies reporting median survivals of 12–15 months. Even more survival variation exists in phase II studies and this disparity is most frequently due to prognostic factors and not individual regimens. Thus, better tools are needed to predict survival both for individual pts and to balance phase III trials. Nomograms have utility in predicting short- and long-term outcome in muscle-invasive UC treated by surgery but they have not been explored in more advanced UC. Methods: We identified 308 pts with metastatic and/or unresectable UC treated on prospective phase II MSKCC protocols of cisplatin-based therapy containing 3–5 total chemotherapy agents. 203 pts received methotrexate, vinblastine, doxorubicin and cisplatin (MVAC), 45 had ifosfamide, paclitaxel and cisplatin (ITP) and 60 pts received doxorubicin plus gemcitabine (AG) followed by ITP (AG-ITP). Survival distributions were compared across trials. Pre-treatment characteristics were then assessed for impact on survival and a nomogram from a fitted Cox model was created to predict 1-yr, 2-yr, 5-yr and median survival. Results: No difference in median survivals were seen among the 3 regimens; median survival was 14.8 months for MVAC, 18.0 months for ITP and 16.1 months for AG- ITP (p=NS). Median survival for all pts was 12.99 months; 268 pts died and 40 pts were censored. 288 pts had all pre-treatment data. Characteristics most associated with survival included visceral metastases (present versus absent, p=.00001) and Karnofsky poor performance status (≥ 80 versus < 80, p= .0005) followed by hemoglobin (normal versus < normal, p=.01) and albumin (actual values, p<.02). These characteristics were then used to construct a nomogram utilizing all 4 factors to predict probabilities of 1-yr, 2-yr, and 5-yr survival. Conclusions: The number and sequence of drugs utilized in cisplatin-based chemotherapy did not substantially impact survival of pts with advanced UC. A nomogram of pre-treatment clinical factors can predict probability of pt survival at 1 yr, 2yrs, and 5 yrs. This nomogram may also be useful to balance treatment arms in phase III trials. No significant financial relationships to disclose.

scholarly journals A Review of Docetaxel: Its Use in the Treatment of Gastric Cancer

2010 ◽  
Vol 2 ◽  
pp. CMT.S5191
Author(s):  
Alessandro Inno ◽  
Michele Basso ◽  
Alessandra Cassano ◽  
Carlo Barone
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Phase Iii ◽  
Poor Performance Status ◽  
Phase Ii Studies ◽  
Combination Regimens

Docetaxel, a member of the taxane family, promotes cell death by binding β-tubulin and has demonstrated activity against several human malignancies, both as a single agent and in combination therapy. It has been approved in Europe and the US as front-line treatment for advanced gastric cancer in combination with cisplatin and fluorouracil (DCF regimen). This approval was based on the results of a pivotal study (V325) which demonstrated that the addition of docetaxel to the reference regimen of cisplatin and fluorouracil improves overall survival and progression-free survival with a better quality of life despite increased toxicity (mainly haematological). Modifications of DCF regimen have been successfully investigated as a means of making the treatment more tolerable and suitable also for elderly patients or patients with poor performance status. Emerging data from several phase II studies suggest that other docetaxel-based combination regimens with anthracyclines or irinotecan have interesting activity with acceptable toxicity profiles, but the true efficacy of these regimens needs to be assessed in large randomized phase III studies. Thus, the best docetaxel-containing regimen has yet to be identified. Docetaxel also represents a good candidate for combination with novel molecular target agents. In light of the high response rates observed in phase II-III studies, a docetaxel-based chemotherapy regimen might also be considered a treatment option as perioperative or adjuvant therapy in potentially curable gastric cancer and further studies with or without biological agents are eagerly awaited in this setting.

Serum cathepsin B (CB) levels are prognostic in chemotherapy-naive patients (pts) with advanced non-small cell lung cancer (NSCLC) and performance status (PS) of 2

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18036-18036
Author(s):  
J. W. Singer ◽  
F. B. Oldham ◽  
B. Bandstra ◽  
L. Sandalic ◽  
J. Bianco ◽  
...  
Keyword(s):  
Median Survival ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Phase Iii ◽  
Serum Samples ◽  
Protein Levels ◽  
Lysosomal Cysteine Protease ◽  
Phase Iii Trials ◽  
And Performance ◽  
The Impact

18036 Background: CB is an estrogen-influenced lysosomal cysteine protease produced by tumor cells and tumor-associated macrophages; tumor tissue CB protein levels and proteolytic activity are prognostic in NSCLC (Anticancer Res. 2004; 24:4147–61). The prognostic value of serum CB has not previously been evaluated in NSCLC. Here we evaluate the impact of pretreatment CB levels on survival in pts from 2 phase III trials in advanced NSCLC, STELLAR 3 and 4. These trials compared paclitaxel poliglumex (PPX) against commonly used regimens. As the intratumoral metabolic pathway of PPX is characterized by the CB-mediated release of paclitaxel (P) from a polymeric backbone (Ca Chemother Pharm. 2006. Epub ahead of print), correlation of CB levels with PPX efficacy was assessed as well. Methods: Pretreatment serum samples from 450 chemo-naive pts with advanced NSCLC and PS 2 enrolled in STELLAR 3 (P + carboplatin (C) v. PPX + C) (N=315) and STELLAR 4 (vinorelbine or gemcitabine v. PPX) (N=135) were assayed for CB by ELISA (ICON Labs). Values were assessed by quartiles and there was a clear breakpoint at the median. Pts were categorized as high or low CB based on values above or below the median (64 ng/ml). The effect of CB levels on survival was evaluated by log rank for pooled pts from the studies. Results: As detailed in the table , median survival for non-PPX-treated pts was worse if CB was high; in contrast, median survival for PPX-treated pts did not differ by CB level. Pts with high CB receiving PPX showed a trend towards better survival compared to those receiving control regimens. Conclusions: The data suggest that serum CB may be prognostic biomarker for NSCLC. Retrospective analysis suggests a trend towards improved survival in patients with high CB receiving PPX; prospective studies are required to confirm this observation. [Table: see text] No significant financial relationships to disclose.

Multitrial evaluation of progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in previously untreated extensive-stage small cell lung cancer (ES-SCLC): An Alliance-led analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7510-7510 ◽  
Author(s):  
Nathan R. Foster ◽  
Lindsay A. Renfro ◽  
Steven E. Schild ◽  
Mary Weber Redman ◽  
Xiaofei F. Wang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Cox Model ◽  
Progression Free Survival ◽  
Surrogate Endpoint ◽  
Phase Iii ◽  
Least Squares Regression ◽  
Patient Level ◽  
Phase Iii Trials ◽  
Using Data

7510 Background: We previously demonstrated that PFS may be a candidate surrogate endpoint for OS in ES-SCLC using data from 3 randomized trials (Foster, Cancer 2011). Here, we sought to formally assess the patient- and trial-level surrogacy of PFS using data from 9 additional randomized phase II and III trials conducted by the NCI-funded cancer cooperative groups since 1986. Methods: Individual patient data from all 12 trials (3178 patients: 9 phase III and 3 phase II) were pooled. OS was the primary endpoint in all phase III trials; 3 phase III and 1 phase II trial were positive per protocol. Patient-level surrogacy (Kendall’s tau) was assessed using the Clayton copula bivariate survival model. Trial-level surrogacy was assessed via association of the log hazard ratios on OS and PFS across trials, including: weighted (by trial size) least squares regression of Cox model effects (R² WLS) and weighted (by trial size) correlation of the copula effects (R² Copula). One trial had 4 treatment arms thus 14 total two-arm comparisons were made. Results: With a median follow-up of 41.8 months in the 106 patients still alive, the median OS and PFS across trials were 9.7 months (95% CI: 9.5, 9.9) and 5.7 months (95% CI: 5.5, 5.8), respectively. There were 3120 PFS events in total (2564 disease progressions and 556 deaths without progression). The median time from progression to death was 4.1 months (95% CI: 3.9, 4.3). PFS showed modest association with OS at the patient-level (tau= 0.56) and at the trial-level (R² WLS = 0.58; R² Copula (standard error) = 0.55 (0.29)). The 95% CIs for the predicted HR for OS given observed HR on PFS under a weighted leave-one-out prediction always included the observed HR for OS; however such intervals were wide, suggesting uncertainty on the practical use of PFS as a surrogate for OS in this setting. Conclusions: PFS failed to demonstrate surrogacy for OS in ES-SCLC based on this large pooled analysis. Given that the difference in the median PFS and OS is less than 6 months, we recommend using OS as the primary endpoint in phase III trials of previously untreated ES-SCLC.

Safety summary of panitumumab (pmab) in combination with chemotherapy (ctx) from four clinical trials in patients (pts) with metastatic colorectal cancer (mCRC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15005-e15005
Author(s):  
T. J. Price ◽  
M. Peeters ◽  
J. Douillard ◽  
E. Mitchell ◽  
A. Cohn ◽  
...  
Keyword(s):  
Phase Ii ◽  
Safety Data ◽  
Data Monitoring Committee ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Two Phase ◽  
Phase Ii Studies ◽  
Study Results ◽  
Phase Iii Trials ◽  
Phase Iii Studies

e15005 Background: Pmab is a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody approved in the US and EU (wild-type KRAS) as monotherapy for pts with mCRC. Safety data from 4 studies (Siena et al ASCO 2008; Peeters et al ASCO 2008; Cohn et al ASCO 2008; Mitchell et al WORLD GI 2008) of pmab in combination with ctx are summarized. Methods: Two studies are single-arm, phase II trials and two are randomized, phase III trials with pooled, blinded safety data that include ctx-controls. All studies were multicenter. Common pt eligibility criteria included: diagnosis of mCRC with measurable disease per modified RECIST criteria, age ≥ 18 years, and adequate hematologic, renal, hepatic, and metabolic function. All studies required pts to receive FOLFOX, FOLFIRI, or irinotecan ctx in combination with pmab. Pts received pmab 6.0 mg/kg Q2W with FOLFOX Q2W or FOLFIRI Q2W, or pmab 9.0 mg/kg Q3W with irinotecan Q3W. Results from planned interim analyses are available for 3 studies, and results from the final analysis are available for one study. Results: Among the 4-study safety data, 1213 pts received pmab + ctx; 703 pts received pmab + FOLFIRI, 455 pts received pmab + FOLFOX, and 55 pts received pmab + irinotecan. Approximately 1,200 pts were enrolled in each phase III study, and data are available from 1,003 pts who received pmab + ctx and 997 pts who received ctx alone. All pts in the phase III studies, regardless of treatment group, were included in the pooled, blinded interim analysis sets monitored by the data monitoring committee for each study. Safety results for the two phase II studies of pmab + ctx and two phase III studies of pmab ± ctx are summarized (Table). Conclusions: Phase II data are consistent with expectations, and phase III trials are ongoing. A consistent safety profile was observed across studies. [Table: see text] [Table: see text]

scholarly journals Most ASH Abstracts Reporting Phase II Studies Lead to Peer-Reviewed Publications, but Less Than 50% of "Positive" Abstracts Lead to Phase III Investigations: An Analysis of 371 Abstracts 2013 - 2015

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4040-4040
Author(s):  
David Cucchi ◽  
Tobias Polak ◽  
Gert J. Ossenkoppele ◽  
Jacob M. Rowe ◽  
Elihu H. Estey
Keyword(s):  
British Journal ◽  
Randomized Trial ◽  
Publication Bias ◽  
Phase Ii ◽  
Phase Iii ◽  
Positive Phase ◽  
Phase Ii Studies ◽  
Phase Iii Trials ◽  
Positive Results ◽  
Reporting Phase

Abstract Reports of "positive" results in early phase trials as presented at ASH presumably herald therapeutic advances, or at a minimum, a larger, potentially confirmatory, randomized trial. However, the predictive value of an ASH abstract reporting positive results in AML for subsequent clinical utility seems low (Estey 2006, ASH). Furthermore, not all results presented at ASH are published in peer-reviewed journals, and selectively publishing positive results leads to publication bias. Moreover, truly negative studies may be scientifically more rigorous and accurate than positive studies given the unequivocal findings. The extent of publication bias is unknown as is the frequency with which positive or negative abstracts lead to subsequent investigation in phase III and the reasons why positive phase II studies might not progress to phase III. We downloaded all 2013 - 2015 ASH abstracts (N = 17,251) and evaluated all abstracts reporting phase II clinical trials (N = 371) of novel drugs and therapeutic regimens presented at ASH in these years, covering investigational treatments of MM, CLL, AML, DLBCL, MDS, NHL, ALL, CML, MCL, SLL, other lymphomas and POEMS. We first scored abstracts "positive", "negative" or "inconclusive". Criteria for a positive abstract were words/phrases such as "encouraging", "promising", "could represent a novel therapeutic option" and "warrants investigation in a randomized trial". Negative abstracts included terms such as "does not support further research" and "demonstrates no clinical activity". The remainder were scored as inconclusive. Using this approach, we scored 296/371 (80%) abstracts as positive, 37/371 (10%) as negative, and 38/371 (10%) as inconclusive. 292/371 abstracts (79%) were published in peer-reviewed journals. The abstract conclusion (positive, negative or inconclusive) was not associated with publication in a peer-reviewed journal. Most frequently, studies were published in Blood (34/292 [11.6%]) and British Journal of Haematology (39/292 [13.4%]) . In Blood, 91% (31/34) of the studies were positive. British Journal of Haematology published significantly more negative studies than Blood (26%, Fisher Exact p = 0.02). Abstracts reporting studies with larger sample sizes tended to be published more often (p = 0.066). Differences exist between the abstract conclusion and later peer-reviewed publications. Of positive ASH abstracts, 6% changed to a negative conclusion in the peer-reviewed publication. Similarly, 6.5% of the initial negative abstract later reversed to a positive conclusion. 53% of positive abstracts did not lead to phase III studies, as registered on clinicaltrials.gov. Subsequently, regimens described in positive peer-reviewed publications did not proceed to phase III research in 48%. To explore why, we sent questionnaires to the first and/or last authors of positive studies not prompting phase III trials. 52% responded. Failure of positive phase II trials to proceed to phase III was due to the decision by the pharmaceutical company to halt clinical investigation (44%), lack of any intent to study the drug in phase III in the first place (40%), insufficient funding (35%), insufficient efficacy (despite the "positive" abstract; 33%) and safety concerns (4%) (Figure). Additional reasons for not proceeding to phase III were the availability of newer regimens, the rarity of the disease, or when regulatory approval had already been obtained after phase II. In conclusion, "positive" and "negative" ASH abstracts are published as full papers equally often, although the positive ones may be published more often in journals with higher "impact factors". More than half of the regimens presented in positive ASH abstracts remain unevaluated in randomized phase III trials. A separate problem is the likely tendency to disproportionately submit (and/or accept) positive, rather than negative, studies to ASH in the first place. We believe our findings raise issues in clinical research that may not be in the best interest of patients. This demands more consideration than it currently receives. Figure 1 Figure 1. Disclosures Ossenkoppele: Astellas: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Abbvie, AGIOS, BMS/Celgene Astellas,AMGEN, Gilead,Servier,JAZZ,Servier Novartis: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Gilead: Consultancy, Honoraria. Rowe: Biosight Inc.: Consultancy.

Characteristics of a phase II study that predict for a positive phase III trial—A study of 383 clinical trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6604-6604
Author(s):  
S. M. Ueda ◽  
V. E. Sugiyama ◽  
C. Stave ◽  
J. Y. Shin ◽  
B. J. Monk ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Predictive Factors ◽  
Phase Ii Study ◽  
Phase Iii ◽  
Positive Phase ◽  
Phase Iii Trial ◽  
Phase Iii Clinical Trials ◽  
Phase Ii Studies ◽  
Phase Iii Trials

6604 Background: To identify the characteristics of a phase II study that predict for a subsequent positive phase III trial. Methods: All phase II studies and subsequent phase III clinical trials on biologics in advanced cancers published from 1985 to 2005 were extracted. Chi-square test and logistic regression models were used for analyses. Results: 383 phase III clinical trials and their preceding phase II studies were identified. 183 (47.8%) phase III trials were “positive” and 200 (52.2%) were negative. 220 trials (57.4%) used biologics alone and 162 (42.3%) used a combination of biologics and chemotherapy. Over the study periods 1985–1990, 1991–1995, 1996–2000, 2001–2005, the percentage of phase II studies that led to positive phase III trials increased from 37.7% to 33.3% to 56.0% to 76.8% (p<0.001). The interval between the publication of phase II and III studies, 0.5–5, 6–10, 11–15, and 16–20 years were also associated with the success of phase III trial, 55.6%, 42.2%, 32.6%, and 10.0%, respectively (p<0.001). Phase II studies from multiple rather than single institutions were more likely to have a successful trial (60.4% vs. 39.4%; p<0.001). The percent of successful trials from pharmaceutical companies was significantly higher compared to academic, cooperative groups, and research institutes (89.5% vs. 44.2%, 45.2%, 46.3%; p=0.002). The publication of the phase II studies in journals with an impact factor of 8 or greater compared to those less than 8 was also predictive (44.1% vs. 58.0%; p=0.024). Phase II studies with a lower attrition rate were also associated with a positive phase III trial (61.1% vs. 41.8%; p=0.025). On multivariable analysis, all factors, except for journal impact factor, were independent predictive factors for a positive phase III trial. Conclusions: In phase II biologic studies, characteristics such as larger number of patients, more recent year of study, multiple vs. single institution participation, shorter time period between publication of phase II to phase III trial, and lower rate of attrition were predictive factors of success in a phase III trial. Investigators need to be cognizant of these phase II study characteristics before designing phase III trials. No significant financial relationships to disclose.

Analysis of Phase II Studies on Targeted Agents and Subsequent Phase III Trials: What Are the Predictors for Success?

2008 ◽  
Vol 26 (9) ◽  
pp. 1511-1518 ◽  
Author(s):  
John K. Chan ◽  
Stefanie M. Ueda ◽  
Valerie E. Sugiyama ◽  
Christopher D. Stave ◽  
Jacob Y. Shin ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Iii ◽  
Targeted Agents ◽  
Phase Ii Studies ◽  
Phase Iii Trials ◽  
Subsequent Phase

Phase II diaziquone-based chemotherapy trials in patients with anaplastic supratentorial astrocytic neoplasms.

1987 ◽  
Vol 5 (3) ◽  
pp. 464-471 ◽  
Author(s):  
S C Schold ◽  
M S Mahaley ◽  
N A Vick ◽  
H S Friedman ◽  
P C Burger ◽  
...  
Keyword(s):  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Phase Iii ◽  
Important Distinction ◽  
Histologic Diagnosis ◽  
Anaplastic Gliomas ◽  
Phase Iii Trials ◽  
Survival Differences ◽  
Astrocytic Neoplasms

We treated 103 patients with histologically confirmed anaplastic supratentorial astrocytic neoplasms with either diaziquone (AZQ) and carmustine (BCNU) or AZQ and procarbazine. There were 74 patients with glioblastoma multiforme (GBM) and 29 patients with anaplastic astrocytoma (AA). AZQ plus BCNU produced partial (PR) or unequivocal responses in seven of 32 (21.9%) patients with GBMs and three of ten (30%) patients with AAs. Two patients with GBMs (6.3%) and five patients with AAs (50%) showed stable disease (SD). AZQ plus procarbazine produced PRs or unequivocal responses in five of 42 (11.9%) patients with GBMs and nine of 19 (47.4%) patients with AAs. Eight patients with GBMs (19%) and one patient with an AA (5.2%) showed SD. In addition to histologic diagnosis, only the Karnofsky performance-status (KPS) rating independently influenced response and survival. Differences in response rates between the two regimens were not significant, although estimated median survival after adjusting for performance status was slightly better with AZQ plus BCNU than with AZQ plus procarbazine (P = .031). Neither age nor prior chemotherapy were significant independent risk factors. Toxicity was mild and primarily hematologic. We conclude that these AZQ-based regimens have activity in patients with recurrent anaplastic gliomas, but that they are not clearly superior to other agents in current use. The histologic diagnosis of GBM is associated with a significantly worse prognosis than AA, and we believe that this important distinction must be recognized in phase II as well as phase III trials.

Bortezomib + gemcitabine (Gem)/carboplatin (Carbo) results in encouraging survival in advanced non-small cell lung cancer (NSCLC): Results of a phase II Southwest Oncology Group (SWOG) trial (S0339)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7017-7017 ◽  
Author(s):  
A. M. Davies ◽  
J. McCoy ◽  
P. N. Lara ◽  
P. H. Gumerlock ◽  
J. Crowley ◽  
...  
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Stage Iiib ◽  
Phase Iii ◽  
Survival Times

7017 Background: Bortezomib (PS-341), a small molecule proteasome inhibitor, has single agent activity in NSCLC and potentiates Gem/Carbo in pre-clinical models in a sequence-specific manner (Mortensen, Cancer Chem Pharm, 2004). A phase I trial of Gem/Carbo + PS-341 in patients (pts) with advanced NSCLC yielded an encouraging response rate of 48%. Here we describe the results of a SWOG phase II study of this regimen in advanced NSCLC. Methods: 114 eligible chemonaive stage IV and selected stage IIIB (pleural effusion) NSCLC pts received Gem 1000 mg/m2 on days 1, 8 and Carbo AUC 5 on day 1, followed 1 hour later by PS-341 1.0 mg/m2 on days 1, 4, 8, 11, with cycles repeated every 3 weeks. Non-progressing pts could continue PS-341 alone after 4 cycles. Results: Pt characteristics: Median age: 64 years; Sex M/F = 68/46; Performance status 0/1 = 50/64; stage IIIB/IV = 13/101. Response rate: 20% (95% CI 13–29%); 66% (95% CI 56–75%) had stable disease. At a median follow-up of 13 months, progression free and median survival times were 5 months (95% CI 3.5–5.3) and 11 months (95% CI 8.2–12.5). One-year survival was 46% (95% C.I. 37–55%). Most common grade 3/4 toxicities: neutropenia (52%), thrombocytopenia (63%), and fatigue (13%). Ongoing correlative studies are examining markers of proteasome inhibition (Bcl2 family, NFKB, IKB) and hypoxia (PAI-1, VEGF, OPN, HIF-1) in tumor tissue and surrogate specimens. Conclusions: The 11 month median survival achieved with the addition of PS-341 to Gem/Carbo in this phase II study is unprecedented in prior SWOG trials in advanced NSCLC, and does not appear to be explained by altered patient characteristics. The toxicity profile of this regimen is favorable. A phase III trial of Gem/Carbo ± Bortezomib in advanced stage NSCLC is under development. Supported by CA38926, CA32102. No significant financial relationships to disclose.

Randomized phase II trial of irinotecan plus cisplatin (IP) versus irinotecan, cisplatin plus etoposide (IPE) every three weeks in patients with extensive disease small cell lung cancer (ED-SCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7087-7087
Author(s):  
I. Sekine ◽  
H. Nokihara ◽  
K. Takeda ◽  
Y. Nishiwaki ◽  
K. Nakagawa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Body Weight Loss ◽  
Complete Response ◽  
Phase Iii ◽  
Antitumor Effects ◽  
Pilot Studies ◽  
Randomized Phase Ii ◽  
Phase Iii Trials ◽  
Grade 3

7087 Background: A promising complete response rate and median survival time were obtained in our previous phase II study of IPE chemotherapy repeated every 4 weeks in patients with ED-SCLC, but the infusion of irinotecan on day 15 was omitted in 77% of patients. Methods: The objective was to evaluate toxicities and antitumor effects of IP and IPE regimens every 3 weeks and to select the arm for subsequent phase III trials. The primary endpoint was overall survival. Previously untreated ED-SCLC patients aged between 20 and 70 years old with a performance status (PS) of 0–2 were randomized to receive either IP (I 60 mg/m2 days 1, 8 and P 60 mg/m2 day 1) or IPE (the same dose of IP and E 50 mg/m2 days 1–3 with G-CSF support) every 3 weeks for 4 cycles. The projected sample size was 110 patients (Liu’s Selection design for pilot studies on survival). Results: From March 2003 to May 2005, 53 patients (43 males/10 females, median age 63) were randomized to IP and 57 patients (48 males/9 females, median age 62) to IPE. Body weight loss and PS were well balanced between the arms. Full cycles were administered in 75% of patients in the IP and in 67% in the IPE arm. Dose reduction was required in 17% of patients in the IP and 28% in the IPE arm. Grade 3–4 neutropenia, anemia and thrombocytopenia were observed in 53%, 34% and 4% of patients in the IP, and 93%, 45%, and 23% of patients in the IPE arm, respectively. Grade 3–4 infection, malaise, anorexia, and diarrhea were noted in 15%, 2%, 0%, and 15% of patients in the IP, and 30%, 11%, 15%, and 24% of patients in the IPE arm, respectively. No treatment related death occurred. Complete and partial responses were noted in 8% and 68% of patients in the IP, and 11% and 75% of patients in the IPE arm, respectively. Conclusion: Toxicity was more severe, but tumor responses seemed better in the IPE arm. The survival analysis will be carried out in April 2006. No significant financial relationships to disclose.

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