Updated analysis of a phase II study (20060314) of panitumumab (pmab) with FOLFIRI as first-line treatment of patients (pts) with metastatic colorectal cancer (mCRC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4085-4085
Author(s):  
R. Greil ◽  
H. Letocha ◽  
E. Gamelin ◽  
J. Thaler ◽  
R. Hofheinz ◽  
...  
Keyword(s):  
Adverse Event ◽  
Combination Therapy ◽  
Phase Ii ◽  
Interim Analysis ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
First Line ◽  
Kras Status ◽  
Ecog Ps

4085 Background: The fully human anti-epidermal growth factor receptor monoclonal antibody pmab, has proven monotherapy activity in chemotherapy refractory mCRC pts with wild-type KRAS-expressing tumors. This first-line, single-arm phase II study is prospectively evaluating whether KRAS status predicts response to treatment when pmab is combined with FOLFIRI. Methods: In this ongoing study, pts with histologically confirmed mCRC (no prior systemic treatment) and ECOG PS 0–2 were enrolled at 36 sites across Europe. Pmab (6mg/kg) and FOLFIRI are administered every 2 weeks. The primary endpoint is objective response rate; secondary endpoints include disease control rate, duration of response, time to response, progression-free survival, time to progression and safety. Results: Data cut-off for the initial interim analysis was 27 June 08 and pending approval of protocol amendment 2, the cut off date for 16 week response rate is 15 Oct 08. Of the 154 pts enrolled, 68% are male; median age is 64 yrs (range, 21–84) and the majority (95%) of pts had ECOG PS 0–1. All pts have received at least one cycle of study treatment; 18% of pts have received ≤2 cycles of full combination therapy and the median number of cycles received is 6. At time of data cut-off, 112 patients (73%) were still receiving at least one element of combination therapy and 29% had stopped treatment with pmab. The most common reason for discontinuing treatment was disease progression (10%). Median follow-up time was 14.3 weeks for all enrolled pts. A total of 97% of patients had experienced at least one adverse event (any grade) and 55% of patients had experienced a grade 3/4 adverse event. There were four reported grade 5 events (hematemesis, rectal hemorrhage, vena cava thrombosis, general physical health deterioration). At time of interim analysis, tissue samples for KRAS analysis are available for approximately 80% of patients. Conclusions: Combining pmab with FOLFIRI in the first-line setting appears to be a well-tolerated regimen. Response rate at 16 weeks in the overall population and by KRAS status and updated safety will be presented. [Table: see text]

CETUFTIRI, a new combination of UFT with leucovorin (LV), irinotecan, and cetuximab as first-line treatment for patients (pts) with unresectable metastatic colorectal cancer (mCRC): Preliminary results from a multicenter phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4087-4087 ◽  
Author(s):  
J. Bennouna ◽  
R. Faroux ◽  
E. François ◽  
C. Ligeza ◽  
C. El Hannani ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
New Combination ◽  
Line Treatment ◽  
First Line ◽  
Egfr Expression ◽  
First Line Treatment

4087 Background: A phase II study (ASCO 2004) established that the combination of UFT (tegafur-uracil) with LV and irinotecan (TEGAFIRI) could be safely administered to pts with unresectable mCRC, with an objective response rate (ORR) of 34% and a median time to progression (TTP) of 5.7 months. We initiated CETUFTIRI, a phase II study, to evaluate the efficacy and tolerability of cetuximab added to TEGAFIRI in chemonaïve pts with unresectable mCRC. Methods: Patients in this single-stage study were aged =18 years, with histologically or cytologically confirmed, bidimensionally measurable mCRC, ECOG performance status 0 or 1, and adequate bone marrow, renal, and hepatic function. EGFR expression was not an inclusion criterion. Treatment consisted of UFT 250 mg/m2/day d1–14, LV 90 mg/day d1–14, and irinotecan 250 mg/m2 d1 every 3 weeks, plus cetuximab 400 mg/m2 week 1 then 250 mg/m2 weekly thereafter. The primary endpoint was ORR and the planned sample size was 61 pts. The study is now closed to accrual. Results: To date, 48 patients are evaluable for safety and 31 are evaluable for efficacy. Patient characteristics (n=48): median age 65 years (range 45–84 years); ECOG PS 0/1: 73/27%; male 65%; tumor sites: colon 69%; rectum 17%; junction 14%; liver metastasis 83%; lung metastasis 46%; other 27%. Adverse events per patient (n=48) after a total of 230 cycles were: grade G3 mucositis 10%; G3/4 neutropenia 10%; G3 nausea/vomiting 8%; G3 asthenia 6%; febrile neutropenia 6%; G3 hypokalemia 6%; G3/4 anemia 4%; G3 diarrhea 2%; acne-like rash G1/2 50% (G3 4%); infusion- related reaction to cetuximab 6%. Two of 31 evaluable pts had a complete response and 11 had a partial response, for an ORR of 42%; 5 pts had stable disease (16%) and 11 pts had progressive disease (35.5%). An independent radiologist review is planned for all 61 pts included up to December 2006. Conclusions: The CETUFTIRI combination seems to have an acceptable toxicity profile with an attractive objective response rate in the first-line treatment of pts with mCRC. No significant financial relationships to disclose.

Phase II study of nimotuzumab combination with paclitaxel and cisplatin as the first-line treatment in patients with local advanced or metastatic esophageal squamous cell cancer (ESCC): An interim analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14604-e14604
Author(s):  
Xiaodong Zhang ◽  
Ming Lu ◽  
Jifang Gong ◽  
Jing Gao ◽  
Xicheng Wang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Interim Analysis ◽  
Phase Ii Study ◽  
Treatment Plan ◽  
Cell Cancer ◽  
Objective Response ◽  
Line Treatment ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

e14604 Background: Nimotuzumab is a genetically engineered humanized antibody (mAb) that recognizes an epitope located in the extracellular domain of human EGFR. Evidences have shown that nimotuzumab is effective and safe in SCCHN. The combination of paclitaxel/cisplatin (TP) is a standard regimen for advanced or metastatic ESCC. This open uncontrolled phase II study was designed to determine the efficacy and safety of nimotuzumab in combination with TP as the first-line treatment in advanced ESCC. Methods: All patients have histology/cytology confirmed advanced or metastatic ESCC with ECOG PS 0-2. The treatment plan is as the following: paclitaxel administered intravenously (IV) 175 mg/m2 on d1 and cisplatin IV 30-35mg/ m2/d on d1-2, every 21 days for 6 cycles, and nimotuzumab IV 200mg weekly. For patients with stable disease (SD) and better, nimotuzumab will be given continuously after 6 cycles of TP. The primary endpoint is objective response rate (RR) with 56 patients enrollment (target RR >60%); secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety/ tolerability. The coordinations between EGFR and ERCC1 with response of treatment will be analyzed. Results: Up to date, 25 patients (male/female, 20/5; median age 58) have been enrolled. All patients were evaluated for toxicity and 22 are evaluable for response. 14 (63.6%) had a confirmed partial response (PR) and 7 (31.8%) had SD as their best responses with disease control rate of 95.4%. Only one patient had progressive disease (PD). Grade 3 or 4 neutropenia, neutropenic fever and anemia occurred in 52.2%, 4% and 13% respectively. Nonhematological toxicities were generally mild with grade 1 or 2 alopecie, hypodynamia, anorexia, nausea, arthralgia, and itch of skin occurring in 80%, 60.9%, 43.5%, 34.8%, 30.4%, and 21.7%. One patient had a grade 3 haematuria. Conclusions: The interim analysis showed that the combination of nimotuzumab with TP is tolerated reasonably well in patients with advanced or metastatic ESCC and encouraging efficacy. The study is ongoing with coordination of biomarkers and response as well.

Weekly association of gemcitabine and topotecan in early recurrent ovarian cancer patients: A French multicenter phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16016-16016
Author(s):  
F. Joly ◽  
T. Petit ◽  
P. Pautier ◽  
E. Guardiola ◽  
F. Mayer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Time ◽  
Phase Ii ◽  
Stable Disease ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Recurrent Ovarian Cancer ◽  
First Line ◽  
Multicenter Phase

16016 Background: A weekly association of gemcitabine and topotecan was tested with the aim of evaluating its efficacy and tolerance in patients recurring after first line platinum and taxane-based chemotherapy. Methods: From December 2004 to April 2006, 77 patients whose disease has progressed within 12 months (time-free interval, TFI) after first line chemotherapy were enrolled in a multicenter phase II study. Primary endpoint was overall response rate (ORR). Gemcitabine (1000 mg/m2) and topotecan (2.5 mg/m2) were given day 1, 8 and 15 (q 28 d) for 6 to 9 cycles. Tumor response was assessed according to RECIST or Rustin criteria. Clinical response was assessed using symptoms improvement in responders and patients with stable disease. Follow-up was updated December 2006. Results: Initial characteristics were: median age 63 years (38 to 80), WHO PS 0–1 93%, serous histology 85%, TFI < 6 months 45%, measurable disease 71%. Four cycles (1 to 8) were administered in average. The only major toxicity was neutropenia (Grade 3 and 4 in 17% and 6% of patients) with one febrile neutropenia; one toxic death (pneumopathy) was observed. 34% of cycles were incomplete (d8 and/or d15 not administered) because of grade 1–2 thrombopenia or grade 1–4 neutropenia. Lenograstim and erythropoietin were administered in 14% and 34% of patients, respectively. Sixty-six (86%) patients were evaluable for response (2 cycles administered). The ORR was 14% (CR=3%, PR=11%); there were 53% of stable disease. ORR was 7% and 20% in patients with TFI < 6 months and = 6 months, respectively. Symptoms were improved in 18 (64%) of 28 patients and pain in 11 (39%) of 28 patients. Median event-free survival time was 3.7 months. Median overall survival time was 12.3 months (7.5 and 15.6 months in patients with TFI < 6 months and = 6 months, respectively; p=0.0244). Conclusions: In resistant/refractory ovarian cancer, weekly gemcitabine and topotecan is associated with low objective response rate but with a high proportion of stable disease and symptoms control leading to acceptable quality of life. No significant financial relationships to disclose.

Bi-weekly administration of capecitabine + oxaliplatin (Xelox-2) in first-line treatment of advanced colorectal cancer (ACRC): A phase II study of the Gruppo Oncologico dell’Italia Meridionale (GOIM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15066-e15066
Author(s):  
P. Fedele ◽  
G. Di Maggio ◽  
S. Leo ◽  
L. Nanni ◽  
F. Giuliani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Phase Ii Study ◽  
First Line ◽  
Main Site ◽  
First Line Therapy ◽  
Ecog Ps

e15066 Introduction: FOLFOX regimen represents a standard first-line therapy for ACRC pts. Oral capecitabine (XEL) has been shown to be a convenient and well tolerated alternative to intravenous 5-fluorouracil (5-FU) in the treatment of ACRC. Experimental data demonstrated the synergism of XEL with Oxaliplatin (OHP), but the questions about the most appropriate dosage and schedule of capecitabine have not yet been completely resolved. Taking into account these data the GOIM started a phase II study to evaluate the activity and the toxicity of biweekly administration of XEL plus OHP (XELOX-2) in ACRC pts. Methods: Previously untreated pts with histological diagnosis of metastatic colorectal cancer, measurable disease, ECOG PS<2, and age 18–75 yrs entered into this trial. The schedule of treatment was as follows: OHP at 100 mg/mq i.v. on days 1 and XEL at 2,000 mg/mq p.o. in two daily administrations from the 1 to the 7 day, every 2 weeks. RECIST and NCI criteria were employed to determine the activity and the toxicity of this regimen. Results: Fifty-one pts have been enrolled and up to now forty-seven are evaluable for activity and toxicity. The main characteristics of the entered pts were: sex (M/F) 38/13, median age 66,5 yrs (range 54–75 yrs), 28 (55%) single and 23 (45%) multiple site of disease. The main site of disease were liver in 38 pts (75%), lymph-nodes in 17 (33%), lung in 9 (18%). Two CR (4%) and 22 PR (47%), 13 SD (28%) and 10 PD (21%) were observed, with an overall response rate of 51% and a disease control rate (CR+PR+SD) of 79%. Median TTP was 5+ months (range 2–19). A total of 413 cycles were administered. In the evaluable pts the main toxicity rate (G1- 2 vs G3–4) were as follows: thrombocytopenia 51/6, anemia 42/0, neutropenia 15/0, nausea/vomiting 30/2, diarrhea 19/2, neurotoxicity 57/0 and asthenia 30/2. Only one pts presented G4 toxicity (diarrhea). Conclusions: These preliminary data show that the combination of XEL and OHP with a biweekly administration is active and well tolerated in ACRC pts. No significant financial relationships to disclose.

Phase II study alternating mFOLFOX 6 and FOLFIRI (FIREFOX) plus bevacizumab (bev) regimen in first-line treatment of advanced colorectal cancer in Japanese patients (KSCC 0801).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 602-602
Author(s):  
Yutaka Ogata ◽  
Yoshito Akagi ◽  
Yoshihiro Kakeji ◽  
Yasunori Emi ◽  
Eiji Oki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
First Line ◽  
Eligibility Criteria ◽  
Free Survival ◽  
Ecog Ps

602 Background: The Kyushu Study group of Clinical Cancer conducted a phase II study that evaluated the FIREFOX regimen. (KSCC0701, Akagi et al, J Clin Oncol 28:15s, 2010). This study demonstrated the efficacy and mild neurotoxicity of this regimen. The present study evaluated the efficacy and safety of the FIREFOX plus bevacizumab (bev). Methods: Eligibility criteria included histologically confirmed advanced colorectal cancer, ECOG PS 0-2 and adequate bone marrow, renal and hepatic function. Patients (pts) received an alternating regimen of 4 cycles of mFOLFOX-6 plus bev (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, bev 5 mg/kg d1 followed by 400 mg/m2 bolus 5-FU and a 46-hr 2,400 mg/m2 5-FU infusion every 2 weeks) followed by 4 cycles of FOLFIRI plus bev (oxaliplatin replaced with irinotecan 150 mg/m2 d1). This schedule was repeated until unacceptable toxicity or disease progression occurred. The primary endpoint is progression-free survival. (UMIN000001312) Results: Of the 52 pts enrolled from May 2008 to July 2009. Two of the patients did not fulfill the eligibility criteria. M/F, 30/20; median age, 59.5 years (range 37 - 75); ECOG PS 0/1/2, 46/4/0. The median number of administration cycles was 14 (range, 2 - 44). Response rate (RECIST criteria) for CR, PR, SD, PD and NE were 2 (4%), 28 (56%), 14 (28%), 4 (8%) and 2 (4%), respectively. An overall response rate was 60% (95% CI: 45 - 74%). Median progression-free survival was14.2 M (95% CI: 10.6 M-16.3 M) and median overall survival was 27.5 M (95% CI; 22.4 M – not determined). The 2-year survival rate was 56.8%. Of the 52 pts evaluated for toxicity. The most common grade 3-4 adverse events were leukopenia (7.7%), neutropenia (32.7%), anemia (1.9%), fatigue (9.6%), anorexia (13.5%), stomatitis (3.8%), neurotoxicity (3.8%), hypertension (1.9%), diarrhea (7.7%), febrile neutropenia (3.8%), nausea (9.6%), vomiting (5.8%), hypersensitivity (3.8%), and thromboembolism (1.9%). Conclusions: The results of this phase II study show that the FIREFOX plus bev regimen is effective and well tolerated in the first-line treatment of advanced colorectal cancer. The low rate of neurotoxicity is also promising.

Docetaxel and curcuminoids (CCM) combination in patients with castration-resistant prostate cancer (CRPC): A phase II study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16021-e16021
Author(s):  
Hakim Mahammedi ◽  
Mélanie Pouget ◽  
Eloise Planchat ◽  
Herve Cure ◽  
Xavier Durando ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Combination Methods ◽  
Psa Response

e16021 Background: Prostate cancer is a major problem in the aging male population. Docetaxel, the first-line reference treatment in CRPC induces a prostate-specific antigen (PSA) response in 45% of patients and an objective tumor response in 12%. Preclinical studies suggested that curcuminoids inhibit tumor metastasis, invasion and angiogenesis and reverse drug resistance. We wanted to potentiate docetaxel by curcuminoïds in CRPC first line. Our previous phase I study showed the safety and the tolerability of CCM associated to docetaxel for advanced breast cancers. We have conducted in 2009-2010 a phase II study to assess the response of CRPC to this combination. Methods: Patients (n=30) with progressing CRPC and rising PSA were enrolled to receive the experimental treatment. Docetaxel was given in standard conditions (75mg/m², 1h i.v infusion every 3 weeks for 6 cycles + prednisolone) with CCM orally at the dose of 6gr/day (7 days by cycle: d-4 to d+2). The primary endpoint was response rate assessed by biological and paraclinical examinations. The secondary endpoints included safety, time to progression and compliance. Twenty nine patients were evaluable on PSA assessment and 15 on RECIST criteria. Results: 26 patients received the treatment totality and 4 withdrew prematurely. No patient withdrew for toxicity (2 deaths and 2 PSA progressions). A PSA response was observed in 17/29 patients (59%) (4 complete and 13 partial) observed rapidly (before the 3rd cycle) for 15 patients. The median time to subsequent PSA progression (TTP) was 5.8 months. Six patients (40%) had a partial objective response and 9 (60%) a stable disease. The median TTP on targets was 7.85 months (n=13/15). The regimen was well tolerated, with uncommon grade 3/4 toxicity; no adverse event was attributed to CCM. Of 169 cycles, 150 (89%) were completed with perfect compliance. Overall survival was 19 months (mean) and 24 months (median) with 17 events as of december 2012. Conclusions: These results are promising in improving the response rate to docetaxel in terms of both PSA decrease and objective response, with good tolerability and acceptability of CCM. A randomized trial is necessary to confirm this results. Clinical trial information: NCT01012141.

scholarly journals Phase II study of DHP107 (oral paclitaxel) in the first-line treatment of HER2-negative recurrent or metastatic breast cancer (OPTIMAL study)

2021 ◽  
Vol 13 ◽  
pp. 175883592110619
Author(s):  
Sung-Bae Kim ◽  
Jae Hong Seo ◽  
Jin-Hee Ahn ◽  
Tae-Yong Kim ◽  
Seok Yun Kang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Triple Negative ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Line Treatment ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

Background: Standard intravenous (IV) paclitaxel is associated with hypersensitivity/toxicity. Alternative IV formulations have improved tolerability but still require frequent hospital visits and IV infusion. DHP107 is a novel oral formulation of paclitaxel that is approved in South Korea for the treatment of gastric cancer. Methods: This multicenter, phase II study using a Simon’s two-stage design investigated the efficacy and safety of DHP107 200 mg/m2 administered orally twice daily on days 1, 8, and 15 every 4 weeks for the first-line treatment of recurrent or metastatic HER2-negative breast cancer. Results: Thirty-six patients were enrolled and 31 were assessable for efficacy. Patient median age was 57 years (range = 34–81) and 11 (31%) had triple-negative disease. A median of seven cycles (range = 1–28) of DHP107 was administered. Objective response rate was 55% (17 patients), all partial responses, according to the investigator’s decision and independent central review (ICR), and 44% (4/9 patients) in those with triple-negative disease. Disease control rate (partial response and stable disease) was 74% (23 patients) according to the investigator’s decision and ICR. In the intention-to-treat (ITT) population of all enrolled participants, the objective response rate was 50% (18/36 patients). Median progression-free survival was 8.9 months [95% confidence interval [CI]: 5.2–12.3) and median time to treatment failure was 8.0 months (95% CI: 4.2–10.0). DHP107 had an acceptable toxicity profile. All patients experienced treatment-emergent adverse events; the most common adverse events were decreased neutrophil count (81% all grades and 78% grade ⩾ 3) followed by peripheral sensory neuropathy (61% all grades and 8% grade 3). However, there was no febrile neutropenia or sepsis. Conclusion: DHP107 showed promising efficacy and acceptable tolerability in this phase II study and is currently being investigated in the OPTIMAL phase III study (NCT03315364). Trial registration: This trial was registered with ClinicalTrials.gov identifier: NCT03315364.

A phase II study of irinotecan, oxaliplatin, 5-fluorouracil, leucovorin (FOLFOXIRI) as a first-line chemotherapy in metastatic gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4076-4076
Author(s):  
J. Lee ◽  
W. Kang ◽  
S. Lee ◽  
J. Kwon ◽  
H. Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Metastatic Gastric Cancer ◽  
Efficacy And Safety ◽  
First Line ◽  
Grade 3

4076 Background: Previous phase II study showed a high efficacy and safety of FOLFOXIRI (irinotecan, oxaliplatin, 5-fluorouracil, leucovorin) combination chemotherapy in metastatic colorectal cancer. This non-randomized open label phase II study evaluated the efficacy and safety of FOLFOXIRI in metastatic or recurrent gastric cancer patients. Methods: Patients with: histologically proven, bidimensionally measurable, metastatic gastric adenocarcinoma, age 18 - 70 years, with a performance status 0 - 2, no prior chemotherapy or at least 12 months after adjuvant therapy, life expectancy > 3 months, signed written informed consent were eligible. Treatment consisted of irinotecan 150 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 100 mg/m2 day and 5-fluorouracil 2000 mg/m2 as a 48-h continuous infusion starting on day 1, repeated every 2 weeks until unacceptable toxicity, patients’ refusal, or up to 12 cycles. The planned sample size was 48 and the primary endpoint was response rate. Results: From August 2004 to August 2005, 48 patients were prospectively enrolled. The median age was 54 years (24 - 69) and male:female ratio was 1.3:1. In total, 379 cycles were administered with a median of 9 cycles per patient (range, 1–12) and 45/48 patients were evaluable for treatment response. Three patients were not assessable for response due patients’ refusal for further chemotherapy following the first cycle. By per-protocol analysis, the objective response rate was 73.3 % (95% CI, 60.8–85.8) with 2 CRs and 31 PRs. Four patients (9%) had stable disease and 8 patients (18%) had progressive disease. The estimated median survival of all patients was 14.0 months (95% CI, 11.8 - 16.2 ) and the estimated median time-to-progression was 8.9 months (95% CI, 6.7–11.0). In total of 379 cycles administered, most common grade 3/4 toxicities were neutropenia (11% of all cycles) and emesis (12%). Grade 2 peripheral neuropathy occurred in 5 patients. One (2%) patient had severe tumor bleeding and 5 (10%) patients experienced grade 3 diarrhea. Conclusions: FOLFOXIRI combination chemotherapy showed a very promising preliminary anti-tumor activity and was generally well tolerated as a first-line treatment for patients with metastatic gastric cancer. No significant financial relationships to disclose.

scholarly journals Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 39 (9) ◽  
pp. 1020-1028
Author(s):  
David F. McDermott ◽  
Jae-Lyun Lee ◽  
Georg A. Bjarnason ◽  
James M. G. Larkin ◽  
Rustem A. Gafanov ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Clear Cell ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
First Line ◽  
Open Label ◽  
Cell Renal Cell Carcinoma ◽  
Metastatic Rcc

PURPOSE Pembrolizumab, a programmed death 1 inhibitor, demonstrated promising single-agent activity in untreated patients with various cancer types. The phase II KEYNOTE-427 study evaluated efficacy and safety of single-agent pembrolizumab in treatment-naive patients with advanced clear cell renal cell carcinoma (ccRCC; cohort A) and advanced non-ccRCC (cohort B). Results of cohort A are reported. METHODS In this open-label, single-arm phase II study, patients with advanced ccRCC received pembrolizumab 200 mg every 3 weeks for ≤ 24 months. The primary end point was objective response rate by RECIST, version 1.1. RESULTS In the total population (N = 110), median time from enrollment to data cutoff was 35.9 (range, 29.5-40.3) months. Objective response rate was 36.4% with four (3.6%) complete responses and 36 (32.7%) partial responses; disease control rate was 58.2% (95% CI, 48.4 to 67.5). Most patients (68.2%) had a decrease in target lesions, including 30.9% with a reduction ≥ 60%. Median duration of response was 18.9 (range, 2.3-37.6+) months; 64.1% of responders had a response ≥ 12 months (Kaplan-Meier). Median progression-free survival was 7.1 months (95% CI, 5.6 to 11.0). Median overall survival was not reached; 12-month and 24-month overall survival rates were 88.2% and 70.8%, respectively. Durable responses were observed across all International Metastatic RCC Database Consortium categories. Grade 3-5 treatment-related adverse events were reported in 30.0% of patients, of which colitis and diarrhea were most frequent. CONCLUSION Single-agent pembrolizumab showed promising antitumor activity as a first-line treatment in patients with advanced ccRCC, with durable responses across International Metastatic RCC Database Consortium categories. Safety and tolerability profile of pembrolizumab monotherapy was comparable to what has been previously described in other tumor types.

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.

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