Gemcitabine Vinorelbine Research Articles

Economic analysis of a randomized phase III trial of gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer (Italian GEMVIN3/NCIC CTG BR14 trial)

Background/objectiveNon-platinum-based chemotherapy is a potential alternative to platinum doublet therapy for advanced non-small cell lung cancer in selected patients. We determined the cost-effectiveness of gemcitabine/vinorelbine (GEMVIN), versus cisplatin/gemcitabine (PG) or cisplatin/vinorelbine (PV), from a government payer perspective. MethodsResults from a randomized trial of GEMVIN versus PG or PV demonstrated no significant difference in global quality of life (primary endpoint) or overall survival between regimens, but superior progression-free survival for platinum-based regimens. A cost analysis was conducted using direct medical costs of treatment, grade 3 or 4 toxicity management, and investigations for the mean number of cycles per study arm. Costs were calculated using Canadian dollars in 2005, and then in 2013 after drug patent expiry. ResultsIn 2005, GEMVIN was the most expensive regimen ($6868), and PV the least expensive ($4650), with an incremental cost of GEMVIN over PV of $2218. Diagnostic and administration costs did not differ significantly among regimens; GEMVIN had the lowest toxicity costs. The principal cost driver in 2005 was the cost of chemotherapy. In 2013, toxicity and administration costs emerged as major drivers; GEMVIN was less costly than PV and PG, (cost savings of $413 over PV). ConclusionDespite similar outcomes, GEMVIN was more expensive than PV or PG in 2005 because of higher chemotherapy costs. By 2013, after chemotherapy drug patent expiry, GEMVIN became the least costly regimen. Economic considerations in oncology change over time, and should be revisited in policy decisions based on cost.

Neoadjuvant sequential epirubicin and docetaxel followed by surgery-radiotherapy and post-operative docetaxel or gemcitabine/vinorelbine combination based on primary response: a multimodality approach for locally advanced breast cancer

Locally advanced breast cancer (LABC) remains a major clinical issue despite progress achieved in recent years. Herein, we present the mature results of a multimodality treatment program tailoring epirubicin (EPI), docetaxel (DOC) and gemcitabine-vinorelbine (GEV) peri-operatively in LABC. Stage III, Eastern Cooperative Oncology Group-Performance status ≤2 patients were eligible. A biopsy documentation had to be performed before the start of chemotherapy (CT). Treatment consisted of four EPI (100mg/m(2), d1q2w) followed by three DOC (100mg/m(2), d1q3w); surgery 3-4weeks from CT completion, followed by radiation therapy (RT) and CT according to response; partial or complete (PR/CR):DOC, no change or progressive disease (NC/PD):GEV. Primary endpoints were: (a) response and conversion to operability/conservative surgery and (b) overall survival (OS) and time to recurrence (TTR). Fifty-six women, aged 32-75 (median 52years), 24 IIIA and 32 IIIB were enrolled; 53 patients completed the entire program. Toxicity was acceptable and no treatment-related death was observed. clinical response rate (RR) 71.4% (40 patients); clinical complete response rate 33.9% (19 patients). Pathological response rate (RR) 67.8% (38 patients); pathological complete response rate 21.4% (12 patients). 33 (58.9%) and 19 (33.9%) patients, respectively, had radical and conservative operations without increased morbidity. After a median follow-up of 62months, median OS has not yet been reached, while median TTR was 42months. OS was longer in patients with clinical (p=0.004) and pathological response (p=0.002), RT (p<0.0001) and post-operative DOC (p=0.038). TTR was favorably affected by pR (p<0.0001), RT (p<0.0004) and post-operative DOC (p=0.005). Pre-operative CT seemed to be equally active throughout all subgroups according to histology, ER/PR and HER2 status. The treatment program of the present study allowed for the completion of an effective therapy at the cost of acceptable toxicity. The results of this study suggest a central role of CT for LABC and the value of eventually dose-dense, EPI- and DOC-based CT in a large proportion of LABC patients, regardless of biological tumor profile. Furthermore, tumor response (cR, pR) is an important surrogate for patients survival and further therapy management.

Perioperative chemotherapy (CT) with induction sequential epirubicin (EPI) and docetaxel (DOC) followed by surgery and DOC or gemcitabine/vinorelbine (GEN) with radiotherapy for locally advanced breast cancer (LABC)

Perioperative chemotherapy (CT) with induction sequential epirubicin (EPI) and docetaxel (DOC) followed by surgery and DOC or gemcitabine/vinorelbine (GEN) with radiotherapy for locally advanced breast cancer (LABC)

Pulmonary toxicity in patients treated with gemcitabine plus vinorelbine or docetaxel for advanced non-small cell lung cancer: outcome data on a randomized phase II study

Studies with the gemcitabine/vinorelbine (GV) or the gemcitabine/docetaxel (GD) combinations have shown similar efficacy and less toxicity compared to platinum-based chemotherapies, in patients with advanced non-small-cell lung cancer (NSCLC). The present trial was designed to test the efficacy and safety of both, GV and GD, combinations. Chemotherapy-naïve patients (n=39)<or=75 years of age, KPS>or=60% and adequate hematological, renal and hepatic function were randomly assigned to receive G 1,000 mg/m2+either V 25 mg/m2 or D 35 mg/m2 (all of which were administered i.v.) on days 1 and 8 every 21 days. Baseline characteristics were comparable in GV (n=20) and GD (n=19) groups. Results indicated objective response of 7 (35%) vs 6 (31%) patients and median time-to-treatment failure of 120 versus 90 days in the GV and GD arms, respectively. The most common non-hematological toxicities were (GV vs GD): grade 2-4 pulmonary toxicity in 1 (5%) vs 7 (37%); grade 2-3 diarrhea 0 versus 4 (21%) and edema 1 (5%) vs 3 (16%); grade 3-4 hematological toxicities occurred in 3 (15%) vs 1 (5%) patients. Our results indicate that the combination of gemcitabine/docetaxel does not have a favorable safety profile with this schedule of administration, particularly in terms of pulmonary toxicity.

Gemcitabine/paclitaxel compared to gemcitabine/vinorelbine in metastatic breast cancer: An interim analysis

1097 Background: New combinations and strategies have been developed over the past 10 years including new drugs such as taxanes and gemcitabine. It is not clear whether the activity of the gemcitabine-paclitaxel (GP) combination regimen would translate into better progression-free or overall survival (OS) when compared with gemcitabine-vinorelbine (GV) especially in metastatic breast cancer. This study was conducted to evaluate the overall response rate (RR) of GP Vs GV. Secondary objectives included individual responses of GP and GV, time to progression (TTP), time to treatment failure (TTF), OS, and toxicities. Methods: Patients(pts) with histological diagnosis of stage IV or recurrent breast cancer who had PS =2 and measurable disease were randomized to receive GP (Gemcitabine: 1,250mg/m2 D1 &amp; D8- paclitaxel: 175 mg/m2 D1, D1=D28) or GV (Gemcitabine: 1,250mg/m2 D1 &amp; D8 - vinorelbine: 25mg/m2 D1 &amp; D8, D1=D21). Pts received anthracycline and/or capecitabine chemotherapy in adjuvant and/or metastatic setting. Results: Of 47 patients enrolled, 24 patients were randomized to GP arm and 23 to GV arm. 72% of patients were stage IV and 28% recurrent disease. To date, all patients were qualified for safety, TTF, TTP and OS analysis. Hematologic toxicities were: Neutropenia in 23% in GP Vs 17% in GV, Anemia in 12% in GP Vs 9% in GV. Non hematologic toxicities were essentially nausea and vomiting grad 2–3 in 27% in GP Vs 31% in GV. Anti-emetic agents were administrated to decrease them. The Complete Response (CR) was 27% in GP Vs 30% in GV, the Partial Response (PR) was 23% in GP Vs 17% in GV; with an Overall Response Rate (ORR) of 50% in GP Vs 47% in GV. Median TTF in weeks was 12 in GP Vs 14 in GV. Median TTP (weeks) was 14 in GP Vs 19 in GV. Median OS (weeks) was 32 in GP Vs 50 in GV. Conclusions: In our experience, schedules incriminating gemcitabine are efficient and produce clinical benefit and there activities are very interesting. The analysis of the useful of paclitaxel or vinorelbine associated to gemcitabine demonstrates that these associations are active with no significant differences in toxicities. Therefore, the questions are what regimens, for what patients to what high responses in pre-treated metastatic breast cancer. No significant financial relationships to disclose.

Randomized phase II cross-over sequential chemotherapy trial of irinotecan/cisplatin (IP) vs. gemcitabine/vinorelbine (GV) in chemo-naïve patients with stage IIIb/IV non-small cell lung cancer (NSCLC)

7134 Background: To compare the efficacy and toxicity of IP vs. non-platinum-based GV in the treatment of advanced NSCLC, we conducted a randomized phase II trial with planned cross-over to the other regimen upon disease progression (PD) after the first-line therapy. Methods: Eligibility required stage IIIb/IV NSCLC, no prior chemotherapy, measurable disease, ECOG PS 0–2, adequate organ functions, and informed consent. After stratification by gender, stage (IIIB or IV) and performance status (PS: 0–1 or 2), eligible pts were randomized to receive either IP (I 65 mg/m2 &amp; P30 mg/m2 on D1 &amp; 8 q 3 weeks) first then GV (G 900 mg/m2 &amp;V25 mg/m2 on D1 &amp; 8 q 3 weeks) upon PD (Arm A) or GV first then IP upon PD (Arm B). Results: Between 12/2003 and 06/2005, 146 pts were enrolled in either Arm A (n = 75) or Arm B (n = 71). There was no difference in gender (male: 77.3% vs. 81.7%), age (median: 58 vs. 60 yrs), PS (PS 2: 10.7% vs. 8.5%), histology (adenocarcinoma: 72.0% vs. 76.6%) and stage (IV: 88.0% vs. 87.3%). IP tended to generate more responses than GN (42.0% vs. 29.0% as first-line, 30.2% vs. 14.3% as second-line), but there was no difference in total response rate by the treatment arm (Arm A: 45.6%, B: 43.5%). During the first-line therapy, IP caused more G3+ anemia (20.0% vs. 7.1%, p = 0.048), G2/3 nausea/vomiting (41.4% vs. 12.9%, p &lt; 0.001), G2 alopecia (35.7% vs. 10.0%, p = 0.001) than GN while pneumonitis was noted only with GN (11.4%). Toxicity profile was similar after the second-line therapy. Both arms resulted in excellent survival outcome with no significant difference between the Arm A and B (median: 16.5 mo vs. 15.1 mo, p = 0.595). Conclusions: Platinum-based IP regimen seemed to be more effective in terms of response rate. Given the overall survival data and the mild toxicity profile of GV regimen, however, either treatment sequence seems to be acceptable for the treatment of advanced metastatic NSCLC. (Supported in part by NCC grants 0210140 and 0510140). No significant financial relationships to disclose.

Gemcitabine Single or Combination Chemotherapy in Post Anthracycline and Taxane Salvage Treatment of Metastatic Breast Cancer: Retrospective Analysis of 124 Patients

To evaluate the efficacy of gemcitabine-based chemotherapy, particularly in patients with anthracycline- and taxane-pretreated 2(nd)-line or greater metastatic breast cancer, and to compare gemcitabine monotherapy (G) with two gemcitabine-based doublets, gemcitabine/vinorelbine (GV) and gemcitabine/capecitabine (GX). Of 124 consecutive patients who progressed after anthracycline- and taxane-containing chemotherapy, 58 received G alone, 38 received GV, and 28 received GX; their outcomes were analyzed retrospectively. The median number of prior metastatic chemotherapy regimens was 2 (range 0 approximately 4). Visceral metastases were observed in 65 patients (51.4%). The overall response rate was 19.3% (21 partial responses). After a median follow-up period of 21.4 months, the overall survival was 7.6 months (95% CI: 5.5 approximately 9.6 months) and the median time to progression was 3.1 months (95% CI: 2.0 approximately 4.2 months). Compared with monotherapy (G), combination therapy with vinorelbine or capecitabine (GV/GX) was associated with a significantly higher response rate (8.2% vs. 28.3%, p=0.008) and a significantly longer median time to progression (2.8 vs. 3.5 months; p=0.028), but overall survival did not differ between the groups (7.4 vs. 8.2 months, respectively; p=0.54). Most of the adverse treatment-related events were mild to moderate in intensity. The most common adverse event was hematologic toxicity. Multivariate analysis showed that poor performance status and a short disease-free interval were independent prognostic factors for impaired overall survival. The combination of gemcitabine with vinorelbine or capecitabine was an active and well-tolerated treatment option for taxane- and anthracycline-pretreated 2(nd)-line or greater metastatic breast cancer patients, and gemcitabine-based doublets were more beneficial than gemcitabine monotherapy in alleviating symptoms for these patients.

Phase II study of gemcitabine/vinorelbine (GV) as first or second line chemotherapy in patients with metastatic soft tissue sarcoma (STS)

9009 Background: Both single agent gemcitabine and vinorelbine have efficacy for treatment of STS. Combination GV is active therapy for metastatic carcinoma, with acceptable toxicity. This single institution phase II trial has been undertaken to determine response rates and toxicity of combination GV for treatment of metastatic STS. Methods: Pts with PS 0–2, unresectable or metastatic STS, adequate end organ function, and no more than 1 prior regimen were eligible. Gemcitabine at 800mg/m2 was infused over 90 minutes on days 1 and 8 of a 21 day cycle, following vinorelbine at 25mg/m2. Pts with grade 3 or 4 toxicity were subsequently treated at the same doses on days 1 and 15 of a 28 day cycle. Results: An initial 18 pts have been accrued, following standard two-stage design by the method of Simon. Histology was uterine or extremity leiomyosarcoma (LMS) in 9, high grade pleomorphic sarcoma in 2, and 1 each with carcinosarcoma, pleomorphic liposarcoma, malignant peripheral nerve sheath tumor (MPNST), desmoplastic small round cell tumor, rhabdomyosarcoma, and small round cell sarcoma. As expected, toxicity has been moderate. 57 cycles have been administered. No treatment related deaths have occurred. Only 3 grade 4 toxicities have been noted, all hematologic. Of 19 episodes of grade 3 toxicity, 10 have been hematologic. Of the remaining 9, 4 have been treatment related, including cough, nausea, vomiting, and SGPT elevation. 3 pts have experienced clinical benefit defined as partial response (PR) or stable disease for greater than 4 months. There have been two confirmed PRs, one high grade uterine LMS progressing after single agent doxorubicin, and one small round cell tumor recurring within 6 months of completion of a 5 drug Ewing's regimen. One metastatic MPNST has exhibited stable disease for greater than 4 months. Median time to progression has been 4.2 months and median survival 6.25 months. Conclusions: GV appears to be a well-tolerated and potentially effective regimen for first or second line treatment of metastatic STS. Further accrual to this Phase II study is warranted. No significant financial relationships to disclose.

Phase II study of gemcitabine/vinorelbine (GV) as first or second line chemotherapy in patients with metastatic soft tissue sarcoma (STS)

9009 Background: Both single agent gemcitabine and vinorelbine have efficacy for treatment of STS. Combination GV is active therapy for metastatic carcinoma, with acceptable toxicity. This single institution phase II trial has been undertaken to determine response rates and toxicity of combination GV for treatment of metastatic STS. Methods: Pts with PS 0–2, unresectable or metastatic STS, adequate end organ function, and no more than 1 prior regimen were eligible. Gemcitabine at 800mg/m2 was infused over 90 minutes on days 1 and 8 of a 21 day cycle, following vinorelbine at 25mg/m2. Pts with grade 3 or 4 toxicity were subsequently treated at the same doses on days 1 and 15 of a 28 day cycle. Results: An initial 18 pts have been accrued, following standard two-stage design by the method of Simon. Histology was uterine or extremity leiomyosarcoma (LMS) in 9, high grade pleomorphic sarcoma in 2, and 1 each with carcinosarcoma, pleomorphic liposarcoma, malignant peripheral nerve sheath tumor (MPNST), desmoplastic small round cell tumor, rhabdomyosarcoma, and small round cell sarcoma. As expected, toxicity has been moderate. 57 cycles have been administered. No treatment related deaths have occurred. Only 3 grade 4 toxicities have been noted, all hematologic. Of 19 episodes of grade 3 toxicity, 10 have been hematologic. Of the remaining 9, 4 have been treatment related, including cough, nausea, vomiting, and SGPT elevation. 3 pts have experienced clinical benefit defined as partial response (PR) or stable disease for greater than 4 months. There have been two confirmed PRs, one high grade uterine LMS progressing after single agent doxorubicin, and one small round cell tumor recurring within 6 months of completion of a 5 drug Ewing's regimen. One metastatic MPNST has exhibited stable disease for greater than 4 months. Median time to progression has been 4.2 months and median survival 6.25 months. Conclusions: GV appears to be a well-tolerated and potentially effective regimen for first or second line treatment of metastatic STS. Further accrual to this Phase II study is warranted. No significant financial relationships to disclose.

Gemcitabine plus vinorelbine in stage IIIB or IV non-small cell lung cancer (NSCLC): a multicentre phase II clinical trial

A phase II study in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) was carried out to evaluate the clinical activity and toxicity of the chemotherapeutic combination of gemcitabine+vinorelbine (GEM/VNR). Forty-five patients (40 male, 5 female) with a median age of 67 years (range 37–73) and a median ECOG performance status of 1 (range 0–2) were enrolled into the trial. Twenty patients had stage IIIB (two positive supraclavicular nodes and 20 cytologically positive pleural effusion), and 25 had stage IV NSCLC. GEM 1000 mg/m 2 diluted in 250 cc 3 of normal saline was administered iv on days 1, 8, and 15, while VNR was given 30 mg/m 2 on days 1 and 8 every 4 weeks. The median number of courses/patient was 4 (range 3–7). According to an intent-to-treat analysis 2 (4%) patients had a complete response and 16 (36%; 95% CL 22–52%) had a partial response for an overall response rate of 40% (95% CL 26–56%) . Twelve (27%) patients had stable disease and 15 (33%) were considered as treatment failures. Median overall survival of the whole series was 8+ months with 33% of patients alive at 1 year. Toxicity was generally mild. WHO grade 3–4 neutropenia was recorded in 22% of cases, grade 1–3 liver toxicity in 6% of patients and neutropenia-unrelated fever in 9%. This multicentre phase II study suggests that the GEM/VNR combination regimen is an active and well tolerated regimen in patients with stage IIIB/IV NSCLC. Larger studies comparing cisplatin-based regimens to new schedules without cisplatin are warranted.

Gemcitabine + vinorelbine (GV) yields better survival than vinorelbine (V) alone in elderly non-small cell lung cancer (NSCLC) patients. Final analysis of a Southern Italy Cooperative Oncology Group (SICOG) phase III trial

Gemcitabine + vinorelbine (GV) yields better survival than vinorelbine (V) alone in elderly non-small cell lung cancer (NSCLC) patients. Final analysis of a Southern Italy Cooperative Oncology Group (SICOG) phase III trial

Gemcitabine + vinorelbine (GV) vs vinorelbine (V) alone in elderly or frail non-small cell lung cancer (NSCLC) patients. Interim analysis of a SICOG phase III trial

Gemcitabine + vinorelbine (GV) vs vinorelbine (V) alone in elderly or frail non-small cell lung cancer (NSCLC) patients. Interim analysis of a SICOG phase III trial