A phase II trial of combination chemotherapy with irinotecan and amrubicin in pretreated patients with non-small cell lung cancer (NSCLC): Results of Okayama Lung Cancer Study Group Trial 0402

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19029-e19029
Author(s):  
S. Kuyama ◽  
Y. Segawa ◽  
N. Nogami ◽  
K. Kiura ◽  
N. Takigawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Time ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Lung Cancer Study Group ◽  
Grade 3

e19029 Background: We previously conducted a phase I trial of combination chemotherapy with irinotecan and amrubicin for NSCLC and found acceptable toxicity profiles with a favorable efficacy in patients with pretreated NSCLC. The aim of this phase II trial was to further evaluate its efficacy and toxicity in this population with a long-term follow-up. Methods: Primary endpoint was objective response. Patients with NSCLC previously treated with one or two chemotherapy regimens were enrolled in this trial. Irinotecan and amrubicin were both administered on days 1 and 8, every 3 weeks at doses of 100 and 40 mg/m2, respectively. Response and toxicity were assessed according to the RECIST guideline and NCI-CTC for AE v3.0. Results: Thirty-one pretreated NSCLC patients were enrolled between 2004 and 2006. A median number of courses administered was 3 (range: 1 to 6). All patients and courses were assessable for efficacy and safety. Demographics of the patients were as follows: M/F:21/10, Ad/others:21/10, ECOG-PS 0/1:12/19, and smoker/non-smoker:21/10. Platinum-based regimens were commonly used as the prior chemotherapy. Objective response was obtained in 9 of the 31 patients with a response rate of 29.0% (95%CI: 12.1–46.0%). Grade 4 leukopenia and neutropenia were observed in 6 (19%) and 14 (45%) patients, respectively, whereas thrombocytopenia were generally mild. Grade 3 febrile neutropenia was observed in 7 patients (23%), of whom two patients further developed Grade 4 and 5 septic shock each. Other grade 3 or greater non-hematological toxicities included diarrhea, vomiting, pneumonitis, liver dysfunction in 4, 1, 1 and 2 patients, respectively. With a median follow-up time of 24.2 months, median survival time and median progression-free survival time were 14.2 and 4.0 months, respectively. Conclusions: This combination seemed highly effective for pretreated NSCLC with an acceptable toxicity. No significant financial relationships to disclose.

A phase II trial of combination chemotherapy with irinotecan and amrubicin in pretreated patients with non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18111-18111
Author(s):  
Y. Segawa ◽  
N. Nogami ◽  
T. Shinkai ◽  
K. Kiura ◽  
M. Tabata ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Survival Time ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

18111 Background: Amrubicin, a totally synthetic anthracycline, is a topoisomerase II inhibitor and highly effective for non-small cell lung cancer (NSCLC) as a single agent with response rates of 25% to 28%. We previously conducted a phase I trial of combination chemotherapy with irinotecan and amrubicin for NSCLC and found acceptable toxicity profiles with a favorable efficacy in patients with pretreated NSCLC. The aim of this phase II trial was to further evaluate its efficacy and toxicity in this population. Methods: Primary endpoint was objective response. Patients with NSCLC previously treated with one or two chemotherapy regimens were enrolled in this trial. Irinotecan and amrubicin were both administered on days 1 and 8, every 3 weeks at doses of 100 and 40 mg/m2, respectively. Response and toxicity were assessed according to the RECIST guideline and NCI Common Terminology Criteria for Adverse Events v3.0. Results: Thirty-one pretreated NSCLC patients were enrolled between 2004 and 2006. A median number of courses administered was 3 (range: 1 to 6). All patients and courses were assessable for efficacy and safety. Demographics of the patients were as follows: M/F: 21/10, Ad/others: 21/10, ECOG-PS 0/1: 12/19, and smoker/non-smoker: 21/10. Platinum-based regimens were commonly used as the prior chemotherapy. Objective response was obtained in 9 of the 31 patients with a response rate of 29.0% (95%CI: 12.1–46.0%). Grade 4 leukopenia and neutropenia were observed in 6 (19%) and 14 (45%) patients, respectively, whereas thrombocytopenia were generally mild. Grade 3 febrile neutropenia was observed in 7 patients (23%), of whom two patients further developed Grade 4 and 5 septic shock each. Other grade 3 or greater non-hematological toxicities included diarrhea, vomiting, pneumonitis, liver dysfunction in 4, 1, 1 and 2 patients, respectively. At the time of this analysis with a median follow-up time in the surviving patients of 7.5 months, median survival time and median progression-free survival time were 11.9 and 4.0 months, respectively. Conclusion: This combination seemed highly effective for pretreated NSCLC despite the moderate toxicity profiles. Development of efficient patient selection is needed to avoid the serious toxicities. No significant financial relationships to disclose.

Survival analysis of induction cisplatin (CDDP)-docetaxel (DOC)-bevacizumab (BEV) chemotherapy followed by maintenance BEV-pemetrexed (PEM) therapy in advanced nonsquamous non-small cell lung cancer (NonSq NSCLC): A phase II trial from Okayama Lung Cancer Study Group 0903.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19040-e19040
Author(s):  
Naoyuki Nogami ◽  
Katsuyuki Hotta ◽  
Toshiyuki Kozuki ◽  
Hiroshige Yoshioka ◽  
Akihiro Nishiyama ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Stage Iv ◽  
Induction Phase ◽  
Lung Cancer Study Group ◽  
Platinum Based Chemotherapy

e19040 Background: BEV maintenance therapy and PEM maintenance therapy in platinum-based chemotherapy yield a significant survival advantage in CALGB and PARAMUNT trials, respectively, but each agent gave only modest impact on survival. We conducted a phase II trial of CDDP-DOC-BEV therapy followed by maintenance BEV-PEM therapy inchemo-naïve advanced NonSq NSCLC. Methods: Forty-one patients (pts) participated in the induction phase, specified as four cycles of induction CDDP (80 mg/m2), DOC (60 mg/m2) and BEV (15 mg/kg) on day 1 of a 21-day cycle. Pts who had not progressed during CDDP-DOC-BEV received maintenance BEV (15 mg/kg) and PEM (500 mg/m2) on day 1 of a 21-day cycle until disease progression. The primary endpoint was PFS, and the secondary endpoints included OS, toxicity, and response. Survival time was calculated from the date of registration. Results: Pt characteristics were as follows: median age: 62 yrs; 76% male; 32% PS 0; 73% stage IV; 93% Ad; 5% EGFR-mutant and 2% ALK-mutant. At the time of this analysis, 34 pts (83%) discontinued the treatment, mainly due to progressive disease (53%). The principal toxicity was myelosuppression (gr. 4 hematological: 21 pts [51%]), and grs. 3/4 febrile neutropenia was observed in 10 (24%) despite no treatment-related deaths. The objective response rate and disease control rate (DCR, % pts with CR/PR/SD) was 82.9% and 97.6%, respectively. Median follow-up time was 15.6 months, and 1-yr PFS rate was 34.2% with 95% confidence interval (CI) of 20.3-48.5%, which met the primary endpoint. Also, 1-yr OS rate was 75.6% (95%CI: 59.4-86.1%). Exploratory analysis for pts with both EGFR- and ALK-wild-typed NonSq NSCLC (n = 16) demonstrated 1-yr PFS and OS rates of 50.0% (24.5-71.1%) and 87.5% (58.6-96.7%), respectively. Also, pts with maintenance therapy (n = 34) had 1-yr PFS and OS rates of 41.2% (24.8-56.9%) and 82.4% (64.9-91.7%), respectively. Conclusions: CDDP-DOC-BEV followed by BEV-PEM maintenance seems highly effective despite moderately toxic profiles in chemo-naïve pts with advanced NonSq NSCLC. Clinical trial information: UMIN000004127.

Irinotecan, cetuximab, and bevacizumab (CBI) versus irinotecan, cetuximab, and placebo (CI) in irinotecan-refractory metastatic colorectal cancer (mCRC): Results from an ACCRU network randomized phase II trial.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 102-102
Author(s):  
Marla Lipsyc-Sharf ◽  
Fang-Shu Ou ◽  
Matthew B. Yurgelun ◽  
Douglas Adam Rubinson ◽  
Deborah Schrag ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Double Blind ◽  
Cox Proportional Hazard Models ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Line Of Therapy

102 Background: Combination irinotecan and cetuximab is approved for irinotecan-refractory mCRC; it is unknown if the addition of bevacizumab would improve outcomes. We studied the efficacy and safety of CBI compared with CI in patients (pts) with RAS wildtype, irinotecan-refractory mCRC. Methods: In this multicenter, randomized, double-blind, placebo-controlled phase II trial, pts with RAS wildtype mCRC and no prior anti-epidermal growth factor receptor therapy who failed at least 1 irinotecan-based chemotherapy regimen and received bevacizumab in at least 1 prior line of therapy were randomized 1:1 to irinotecan 180 mg/m2 (or previously tolerated dose), cetuximab 500 mg/m2, and bevacizumab 5 mg/kg vs CI every 2 wks until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoint was progression free survival (PFS). Multivariable Cox proportional hazard models stratified by number of prior lines of therapy and bevacizumab receipt in immediate prior line were performed. Secondary endpoints included overall survival (OS), objective response rate (ORR), and adverse events (AEs). The study was closed early in January 2018 for reasons related to accrual and funding after enrollment of 36 out of a planned 60 pts. Results: Between July 2015 and December 2017, 36 pts were randomized (19 to CBI, 17 to CI). 34 pts (94%) were treated with 2 or more prior chemotherapy regimens. Baseline characteristics were similar between arms. Median PFS was 9.7 vs 5.5 mo for CBI and CI arms, respectively (log-rank P =0.76; multivariable HR = 0.64; 95% CI, 0.25-1.66). Median OS was 19.7 vs 10.2 mo for CBI and CI (log-rank P= 0.04; multivariable HR = 0.41; 95% CI, 0.15-1.09). ORR was 37% for CBI vs 12% for CI ( P =0.13). Grade 3 or higher AEs occurred in 47% of pts receiving CBI vs 35% for CI ( P =0.46). Conclusions: In this prematurely discontinued trial, there were non-significant increases in PFS and ORR and a statistically significant 9.5 mo increase in median OS in favor of CBI compared to CI. Further investigation of CBI for treatment of irinotecan-refractory mCRC is warranted. Clinical trial information: NCT02292758.

151 A RANDOMIZED,OPEN CLINICAL TRIAL TO COMPARE THE EFFICACY AND SAFETY OF ANLOTINIB PLUS IRINOTECAN VERSUS IRINOTECAN IN PATIENTS WITH ESCC

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Feng Wang ◽  
Xiangrui Meng ◽  
Hangrui Liu ◽  
Qingxia Fan
Keyword(s):  
Disease Control ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Thyroid Stimulating Hormone ◽  
Disease Control Rate ◽  
Control Group ◽  
Trial Group ◽  
Grade 3

Abstract   The benefit of systemic treatment in esophageal squamous cell carcinoma (ESCC) which has progressed after chemotherapy is still uncertain. Anlotinib (AL3818) is a novel multi-target TKI, inhibiting tumor angiogenesis and proliferation. A phase II trial (NCT02649361) has demonstrated that anlotinib has a durable antitumor activity with a manageable adverse event profile in refractory metastatic ESCC. This study (NCT03387904) aimed at comparing the effects and safety of Anlotinib Plus Irinotecan versus Irinotecan in patients with ESCC. Methods We conducted a prospective randomized, multicenter, phase II trial to compare the efficacy of Anlotinib Plus Irinotecan with Irinotecan in recurrent ESCC patients who had resistance to platinum or taxane-based chemotherapy. Eligible patients were adults with pathologically confirmed recurrent ESCC, and 82 patients were randomized 1:1 to Irinotecan (65 mg/m2/day 1 and day 8) with or without anlotinib (12 mg qd day 1 to 14) of a 21-day cycle till progression or intolerable. The primary endpoint is the disease control rate (DCR) and progression-free survival (PFS) and the secondary end points are objective response rate (ORR) and overall survival (OS). Results Between 13/1 2019 and 20/1 2020, a total of 43 patients were enrolled and randomly assigned to either the anlotinib plus irinotecan (n = 22) or the irinotecan group (n = 21).The mPFS was longer in trial group than in control group (89 days vs 66 days, HR = 0.447, P = 0.055). The Disease control rate (DCR) was 54.5% in trial group and 38.1% in the control group. The treatment-related adverse events (>10%) were fatigue (59.1%), nausea (50.0%), decreased appetite (36.4%), hoarseness (27.3%), thyroid-stimulating hormone elevation (22.7%), diarrhea (9.1%), and decreased lymphocytes count(9.1%) in trial group. Grade 3 AEs included fatigue (4.5% vs 4.8%), nausea (4.5% vs 0%) and diarrhea (4.5% vs 0%) in two groups. Conclusion Anlotinib plus irinotecan was similarly tolerable but prolonged PFS compared to irinotecan monotherapy as a second-line treatment in patients with recurrent ESCC.

scholarly journals Nivolumab and Hypofractionated Radiotherapy in Patients With Advanced Lung Cancer: ABSCOPAL-1 Clinical Trial

2021 ◽  
Vol 11 ◽  
Author(s):  
Hua Ye ◽  
Haowen Pang ◽  
Xiangxiang Shi ◽  
Peirong Ren ◽  
Shangke Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Hypofractionated Radiotherapy ◽  
Advanced Lung Cancer ◽  
Clinical Trial Registration ◽  
Before And After ◽  
Grade 3

BackgroundMore clinical practice need to be performed to verify the toxicity of the hypofractionated radiotherapy (HFRT) combined with PD-1 blockade in lung cancer. This phase I study aimed to investigate the safety and efficacy of nivolumab combined with HFRT in patients with progressive advanced lung cancer following multiline treatment.MethodsWe enrolled 31 patients with advanced lung cancer pathologically confirmed to have progressive disease and treated with first-line or a higher therapy. Selected lesions were treated using HFRT, and nivolumab was administered within 7 days subsequently. Nivolumab was administered once a month following partial remission. Peripheral blood was collected before and after 1 month of treatment to evaluate relevant cytokines between nivolumab responders and non-responders.ResultsOverall, 23 patients who completed the treatment were evaluated. Of them, 9 and 14 patients underwent hypofractionated brachytherapy with 30 Gy in a single fraction via percutaneous interstitial implantation of (192)Ir and 40–50 Gy in 5 fractions via stereotactic body radiation therapy, respectively. The median follow-up period was 11 months. At the 1-year follow-up, no patient developed grade ≥ 3 pneumonitis. The overall objective response and complete remission rates were 39.13% and 13.04%, respectively. The 1-year overall survival and median progression-free survival were 60.9% and 6 months, respectively. The plasma levels of interleukin IL-6, IL-10, and IL-17A were significantly reduced after treatment in nivolumab responders.ConclusionsHFRT could increase the responsivity to nivolumab and reduce its administration frequency. This combination treatment is well tolerated with acceptable toxicity and thus merits further trials to validate benefits.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifier ChiCTR-1900027768.

Phase II trial of vinblastine, ifosfamide, and gallium combination chemotherapy in metastatic urothelial carcinoma.

1994 ◽  
Vol 12 (11) ◽  
pp. 2271-2276 ◽  
Author(s):  
L H Einhorn ◽  
B J Roth ◽  
R Ansari ◽  
R Dreicer ◽  
R Gonin ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Gallium Nitrate ◽  
Major Toxicity ◽  
Metastatic Urothelial Carcinoma ◽  
Grade 3 ◽  
Related Mortality

PURPOSE Phase II trial in metastatic urothelial carcinoma using a novel combination chemotherapy regimen consisting of vinblastine, ifosfamide, and gallium nitrate (VIG). PATIENTS AND METHODS Twenty-seven patients were entered onto this phase II study. Dosages were vinblastine 0.11 mg/kg days 1 and 2, ifosfamide 1.2 gm/m2 days 1 through 5 (with mesna), and gallium 300 mg/m2 as a 24-hour infusion days 1 through 5, with calcitriol (1,25-dihydroxycholecalciferol) 0.5 microgram/d orally starting 3 days before each course (except the first) and continuing throughout gallium administration, plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) (filgrastim) 5 micrograms/kg/d days 7 through 16. Courses were repeated every 21 days for a maximum of six cycles. RESULTS The major toxicity was granulocytopenia. Fifteen patients (55.6%) had grade 3 or 4 granulocytopenia, including eight patients with granulocytopenic fevers. Eleven patients had grade 3 or 4 anemia and four had grade 3 or 4 nephrotoxicity, which was reversible. Other grade 3 to 4 toxicities included hypocalcemia (three patients), thrombocytopenia (two), encephalopathy (one), and temporary blindness (one). There was one treatment-related mortality. Toxicity was more severe in patients older than 70 years and those with prior pelvic irradiation, prior cisplatin adjuvant therapy, or prior nephrectomy. We now decrease VIG by 20% in this patient population. Eighteen patients (67%) achieved an objective response, including 11 (41%) who attained a disease-free status (five with VIG alone and six with subsequent surgery). Median duration of remission was 20 weeks, with five patients still in remission at 22+ to 56+ weeks. CONCLUSION VIG combination chemotherapy is very active in patients with metastatic urothelial carcinoma. Toxicity was significant but manageable.

Phase II Trial of Temozolomide in Patients With Progressive Low-Grade Glioma

2003 ◽  
Vol 21 (4) ◽  
pp. 646-651 ◽  
Author(s):  
Jennifer A. Quinn ◽  
David A. Reardon ◽  
Allan H. Friedman ◽  
Jeremy N. Rich ◽  
John H. Sampson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Chemical Conversion ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Grade 3 ◽  
Experienced Grade

Purpose: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma. Patients and Methods: Temodar was administered orally once a day for five consecutive days (in a fasting state) at a starting dose of 200 mg/m2/d. Treatment cycles were repeated every 28 days following the first daily dose of Temodar. Response criteria used a combination of magnetic resonance imaging and physical examination to evaluate activity. Results: Forty-six patients with low-grade glioma have been treated to date. The objective response rate was 61% (24% complete response and 37% partial response), with an additional 35% of patients having stable disease. Median progression-free survival (PFS) was 22 months (95% confidence interval [CI], 15 to ∞ months) with a 6-month PFS of 98% (95% CI, 94% to 100%) and a 12-month PFS of 76% (95% CI, 63% to 92%). Toxicity observed during the study was limited to only six patients. Three patients experienced grade 3 neutropenia, with a duration greater than 3 weeks in one patient, and two patients experienced grade 3 thrombocytopenia. One patient experienced ≥ grade 4 toxicity, with intracerebral hemorrhage, neutropenia, thrombocytopenia, sepsis, and death. Conclusion:Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.

Preoperative gemcitabine (G) and docetaxel (D) in patients (pts) with stage IB, II, or III non-small cell lung cancer (NSCLC): A phase II trial of the Minnie Pearl Cancer Research Network

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17007-17007 ◽  
Author(s):  
D. R. Spigel ◽  
J. D. Hainsworth ◽  
D. A. Yardley ◽  
H. A. Burris ◽  
D. S. Thompson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Large Cell ◽  
Research Network ◽  
Preoperative Treatment ◽  
Grade 3 ◽  
Intent To Treat ◽  
Ecog Ps

17007 Background: Preoperative chemotherapy may improve outcomes for pts with resectable NSCLC compared with surgery alone. This multicenter community-based phase II trial examined the role of preoperative G/D for pts with resectable NSCLC. Methods: The primary endpoint was to assess the response rate (RR) of G/D in pts with potentially resectable clinical stages IB, II, and selected III NSCLC [T3N1, T1–3N2 (1 nodal station ≤2 cm), T4N0, T4N1 excluding vascular, tracheal, esophageal, vertebral disease, or malignant effusions]. Treatment included: D 30 mg/m2 IV and G 1000 mg/m2 IV D1,8 Q 21D × 3 cycles. Pts were restaged after treatment and resected 3–6 weeks later. Eligibility included: measurable disease, ECOG PS 0–1, adequate organ function, informed consent. Analysis was by intent to treat. Results: Fifty-four pts were enrolled between 4/04 and 9/05. Baseline features include: median age 62 years (42–82); male/female, 44%/56%; ECOG PS 0/1: 50%/50%; adenocarcinoma (28%), squamous (43%), large cell (9%), mixed/not specified (20%); IB (30%), IIA (5%), IIB (19%), IIIA (33%), IIIB (13%). Forty-eight pts (91%) completed preoperative treatment and 32 pts (60%) underwent resection. Grade 3/4 hematologic and non-hematologic toxicities were limited to neutropenia (20%) and infection (8%), respectively. All other toxicities were <5%. There were no treatment-related deaths. Complete/partial responses for all pts were observed in 1 pt/16 pts, respectively, for an overall RR of 31% (95% CI 20%–44%). Twenty-five pts (46%) had stable disease, and 11% had progression (6 pts were unevaluable.) No pathological complete responses were observed in 32 resected pts. After a median follow-up of 12 months, actuarial 1-year progression-free survival and overall survival (OS) are 54% and 79%, respectively. Median OS has not been reached. Conclusions: G/D is a well-tolerated preoperative regimen for pts with resectable NSCLC with activity rivaling platinum-based regimens. Further follow-up and additional studies comparing preoperative and adjuvant treatment are needed to assess the benefit of this regimen. [Table: see text]

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1948-1953 ◽  
Author(s):  
J Zalcberg ◽  
M Millward ◽  
J Bishop ◽  
M McKeage ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9000-9000
Author(s):  
Martin Reck ◽  
Tudor-Eliade Ciuleanu ◽  
Manuel Cobo ◽  
Michael Schenker ◽  
Bogdan Zurawski ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Performance Status ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Expression Level ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]

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