Multicenter phase II trial of docetaxel and carboplatin in patients with stage IIIB and IV non-small-cell lung cancer

Belani, Chandra P.; Einzig, Avi I.; Bonomi, Philip; Dobbs, T.; Capozzoli, M.J.; Earhart, Robert H.; Cohen, Lorenzo; Luketich, James D.

doi:10.1023/a:1008342116536

Cited by 43 publications

(29 citation statements)

References 25 publications

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“…Indeed, most patients with any reported neuropathy had it for less than a day, and almost all reported that alopecia was noticed only by the patient. These results compare favorably with those of the four studies discussed above, [27][28][29][30] as well as the Shepherd and Manegold pemetrexed-plus-cisplatin studies. 11,12 The five cases of thrombosis were considered to be disease-rather than treatment-related because multiple studies of pemetrexed both alone and in combination with a platinum, including carboplatin, have reported minimal treatment-induced thromboses.…”

Section: Discussionsupporting

confidence: 74%

“…Indeed, our data and the observed numerically equivalent overall survival in the second-line Phase III pemetrexed ver- [27][28][29][30] Likewise, only 3 (6%) in this study had Grade 3/4 nonhematologic toxicity of any kind as compared with a partial list of toxicities from these other studies such as the 14% and 27% Grade 3/4 nausea and vomiting in the carboplatin plus gemcitabine and cisplatin plus gemcitabine trials, respectively, the 24% Grade 3/4 asthenia in the carboplatin plus docetaxel trial, and Grade 3 anorexia 23%, fatigue 21%, and neuropathy 2% with carboplatin plus paclitaxel. [27][28][29][30] It is especially notable that neuropathy, a side effect that can continue well beyond completion of therapy, and alopecia, a side effect that often causes substantial emotional distress, were mild, transient, and not cumulative. Indeed, most patients with any reported neuropathy had it for less than a day, and almost all reported that alopecia was noticed only by the patient.…”

Section: Discussionsupporting

confidence: 63%

“…26 In addition, compared with the 1-year and median survivals (12.2-14.2 mos and 52-62%, respectively) in 4 Phase II outcomes of representative platinum doublets including cisplatin or carboplatin plus gemcitabine, carboplatin plus paclitaxel, and carboplatin plus docetaxel, there is comparable activity. [27][28][29][30] Although this study did not meet its predefined efficacy endpoint of 14/50 objective responses, the greater than 1-year median survival is comparable to those seen in other Phase II studies of modern platinum-containing doublets. Indeed, our data and the observed numerically equivalent overall survival in the second-line Phase III pemetrexed ver- [27][28][29][30] Likewise, only 3 (6%) in this study had Grade 3/4 nonhematologic toxicity of any kind as compared with a partial list of toxicities from these other studies such as the 14% and 27% Grade 3/4 nausea and vomiting in the carboplatin plus gemcitabine and cisplatin plus gemcitabine trials, respectively, the 24% Grade 3/4 asthenia in the carboplatin plus docetaxel trial, and Grade 3 anorexia 23%, fatigue 21%, and neuropathy 2% with carboplatin plus paclitaxel.…”

Section: Discussionsupporting

confidence: 45%

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Phase II study of pemetrexed in combination with carboplatin in the first‐line treatment of advanced nonsmall cell lung cancer

Zinner

Fossella

Gladish

et al. 2005

Cancer

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BACKGROUNDThe primary objectives of this study were to determine the efficacy and tolerability of a pemetrexed‐carboplatin combination as first‐line therapy in patients with advanced nonsmall cell lung cancer.METHODSEligibility criteria included Zubrod performance status of 0 or 1, Stage IIIB (malignant effusion) or IV disease, and no prior chemotherapy. Treatment was pemetrexed 500 mg/m2 given intravenously and carboplatin area under the serum concentration–time curve = 6 given intravenously on Day 1 every 3 weeks for six cycles; patients could receive additional cycles at the discretion of the treating physician and patient. All patients received folic acid, vitamin B12, and dexamethasone prophylaxis.RESULTSFifty patients (31 men and 19 women) were treated. The median age was 62 years. Ninety‐six percent of patients had Stage IV disease, and 88% had a performance status of 1. The median number of cycles was 6; 15 patients received 8 or more cycles. There was Grade 3/4 neutropenia in 11 (22%) and 2 (4%) patients, respectively; Grade 3/4 thrombocytopenia in 1 (2%) and 0 patients, respectively. Three patients (6%) experienced Grade 3 nonhematologic side effects (diarrhea, neutropenic pneumonia, and fatigue). No patients had sensory neuropathy or alopecia >Grade 1. The partial response rate was 24%, median time to progression 5.4 months, 1‐year survival 56.0%, and median survival 13.5 months.CONCLUSIONSThis is an active, very well‐tolerated regimen. Trials focused on how to integrate this doublet with novel agents are warranted. Cancer 2005. © 2005 American Cancer Society.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionsupporting

confidence: 63%

Section: Discussionsupporting

confidence: 45%

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Phase II study of pemetrexed in combination with carboplatin in the first‐line treatment of advanced nonsmall cell lung cancer

Zinner

Fossella

Gladish

et al. 2005

Cancer

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“…We were interested in the activity of the combination of docetaxel and carboplatin as second-line treatment in NSCLC patients, who were treated with platinum or non-platinum-containing regimens as first-line therapy. In chemotherapy-naive patients the combination of docetaxel and carboplatin was active with response rates between 27 and 44%, and acceptable toxicity [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Phase II study of docetaxel and carboplatin as second-line treatment in NSCLC

Wachters¹,

Putten

Boezen

et al. 2004

Lung Cancer

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“…overall treatment efficacy was favorable, but was not enhanced by COX-2 inhibitors in terms of tumor response (36.0%), OS (13.7 months) and 1-year survival ratio (56.0%). Previous phase II-III trials of docetaxel and carboplatin without COX-2 inhibitors for advanced NSCLC demonstrated that the ORR, OS and 1-year survival rate were 16.0-55.0%, 9.0-13.9 months and 44.0-58.0%, respectively (15,(18)(19)(20). The incidence of adverse events, such as grade 3/4 neutropenia (80.0%) and febrile neutropenia (8.0%), was similar to those previously reported (51.1-79.0 and 3.3-26.0%, respectively).…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2 inhibitors for non-small-cell lung cancer: A phase II trial and literature review

Yokouchi

Kanazawa

Ishida

et al. 2014

Molecular and Clinical Oncology

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Abstract. Several preclinical and clinical studies have demonstrated that cyclooxygenase-2 (COX-2) inhibitors are efficient for the treatment of non-small-cell lung cancer (NSCLC). However, two recent phase III clinical trials using COX-2 inhibitors in combination with platinum-based chemotherapy failed to demonstrate a survival benefit. Thus, validation and discussion regarding the usefulness of COX-2 inhibitors for patients with NSCLC are required. We conducted a prospective trial using COX-2 inhibitors for the treatment of 50 NSCLC patients accrued between April, 2005 and July, 2006. Patients with untreated advanced NSCLC received oral meloxicam (150 mg daily), carboplatin (area under the curve = 5 mg̸ml x min on day 1) and docetaxel (60 mg/m 2 on day 1) every 3 weeks. The primary endpoint was response rate. The response and disease control rates were 36.0 and 76.0%, respectively. The time-to-progression (TTP) and overall survival (OS) were 5.7 months [95% confidence interval (CI): 4.6-6.7] and 13.7 months (95% CI: 11.4-15.9), respectively. The 1-year survival ratio was 56.0%. Grade 3 neuropathy was observed in only 1 patient. We performed tumor immunohistochemistry for COX-2 and p27 and investigated the correlation between their expression and clinical outcome. COX-2 expression in the tumor tended to correlate with a higher response rate (50.0% in the high-and 18.2% in the low-COX-2 group; P=0.092). Based on our results and previous reports, various trial designs, such as the prospective use of COX-2 inhibitors only for patients with COX-2-positive NSCLC, including the exploratory analysis of biomarkers associated with the COX-2 pathway, may be worth further consideration. IntroductionCyclooxygenase-2 (COX-2), the enzyme that converts arachidonic acid to prostaglandins (PGs), is expressed in a number of solid tumors and is associated with carcinogenesis, tumor proliferation, infiltration, metastasis, angiogenesis and resistance to anticancer drugs (1). In lung cancer cells, COX-2, which is particularly overexpressed in adenocarcinoma (2), is considered to be a negative predictor of survival in this subpopulation (3-7). Based on these reports, several clinical trials have been conducted for the potentiation of targeting COX-2 in lung cancer (8).The cyclin-dependent kinase (Cdk) inhibitor p27 plays a critical role in cell cycle regulation from the G1 to the S phase by inhibiting Cdk4/6-cyclin D1 and Cdk2-cyclin E (9). Loss of p27 expression tends to be an unfavorable prognostic factor in patients with non-small-cell lung cancer (NSCLC) (10). Increased p27 expression is attributed to COX-2-independent mechanisms of G0/G1 arrest driven by COX-2 inhibitors (11). Thus, p27 expression may be another predictive factor of the response to COX-2 inhibitors.Taxanes, such as paclitaxel and docetaxel, are microtubule-stabilizing agents that act by interfering with spindle microtubule dynamics, causing cell cycle arrest and apoptosis through activating a number of molecular pathways (12,13). Taxanes are able to drive COX-2...

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Multicenter phase II trial of docetaxel and carboplatin in patients with stage IIIB and IV non-small-cell lung cancer

Abstract: The combination of docetaxel and carboplatin has an acceptable toxicity profile and is active in the treatment of previously untreated patients with advanced NSCLC. This combination is being evaluated in a randomized phase III trial involving patients with advanced and metastatic NSCLC.

Cited by 43 publications

References 25 publications

Phase II study of pemetrexed in combination with carboplatin in the first‐line treatment of advanced nonsmall cell lung cancer

Phase II study of pemetrexed in combination with carboplatin in the first‐line treatment of advanced nonsmall cell lung cancer

Phase II study of docetaxel and carboplatin as second-line treatment in NSCLC

Cyclooxygenase-2 inhibitors for non-small-cell lung cancer: A phase II trial and literature review

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