Methotrexate, vinblastine, doxorubicin and cisplatin combination regimen as salvage chemotherapy for patients with advanced or metastatic transitional cell carcinoma after failure of gemcitabine and cisplatin chemotherapy

Han, Kyung Seok; Joung, Jae Young; Kim, T S; Jeong, In Gab; Seo, Ho Kyung; Chung, Jinsoo; Lee, K H

doi:10.1038/sj.bjc.6604113

Cited by 49 publications

(31 citation statements)

References 29 publications

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“…Various single agents and combinations of agents have been reported as second-line chemotherapy regimens (16)(17)(18)(19)(20)(21)(22)(23). Even in the NCCN guidelines, the second-line chemotherapy data are highly variable and unclear in this setting; thus, no standard therapy exists.…”

Section: Discussionmentioning

confidence: 99%

The combination of paclitaxel and carboplatin as second-line chemotherapy can be a preferred regimen for patients with urothelial carcinoma after the failure of gemcitabine and cisplatin chemotherapy

et al. 2017

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Abstract. There is no established standard second-line chemotherapy after the failure of the first-line cisplatin-based chemotherapy for patients with advanced or metastatic urothelial carcinoma. With regards to second-line chemotherapy, methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) was used from July 2009 onwards, and paclitaxel and carboplatin (TC) was introduced in April 2014 at the National Kyushu Cancer Center. The present study aimed to assess the prognostic factors for overall survival (OS) in second-line treatment that included best supportive care (BSC), and the tolerability and efficacy of TC chemotherapy. In total, 52 patients who were confirmed to have disease progression with first-line gemcitabine and cisplatin (GC) between June 2009 and November 2016 were enrolled in the current study. In addition, 28 patients selected BSC as second-line treatment, while 24 patients received second-line chemotherapy (MVAC, n=8; TC, n=16). The median OS for BSC, MVAC and TC was 2.8, 5.4, and 12.7 months, respectively. The difference between BSC and MVAC was not statistically significant (P=0.596). However, the difference between BSC and TC was statistically significant after Bonferroni correction (P=0.002). Multivariate analyses revealed that anemia [hazard ratio (HR), 7.047; 95% confidence interval (CI), 1.553-35.636; P= 0.011], the presence of visceral metastasis (HR, 4.174; 95% CI, 1.506-13.429; P= 0.005) and second-line treatment (TC HR, 0.296; 95% CI, 0.124-0.636; P= 0.003) were independent prognostic factors. TC achieved an 18.7% overall response rate and a 56.2% disease control rate. Myelosuppression was the most common grade ≥3 toxicity, but no treatment-associated mortalities occurred during the study period. TC was associated with favorable benefits and safety, and may be considered a preferred regimen after the failure of GC.

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Section: Discussionmentioning

confidence: 99%

The combination of paclitaxel and carboplatin as second-line chemotherapy can be a preferred regimen for patients with urothelial carcinoma after the failure of gemcitabine and cisplatin chemotherapy

et al. 2017

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“…In patients progressing on gc or relapsing within 6 to 12 months and still eligible for cisplatin therapy, recent data have shown that a second-line regimen of mvac can offer acceptable outcomes, with an or of 30% and a mds of 10.9 months 87 . The most extensively studied second-line combination regimen is paclitaxel and gemcitabine.…”

Section: Multi-agent Second-line Therapymentioning

confidence: 99%

First- and Second-Line Therapy for Metastatic Urothelial Carcinoma of the Bladder

2011

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but little improvement has been achieved in the outcomes of patients with advanced or metastatic disease. Almost 90% of those patients eventually succumb to their cancer.For patients who relapse after first-line chemotherapy, the prognosis is generally poor. To date, there is no real consensus on how to best treat these patients, and most of the available evidence stems from small phase ii trials that have mostly failed to show survival benefit over supportive care. The present review provides an update on the management of metastatic bc, with a focus on first-line and secondline therapies. FIRST-LINE THERAPY Single-Agent TherapySingle-agent therapy has generally failed to provide adequate results in patients with advanced bc. In a phase iii trial of patients randomized to receive either cisplatin alone or in combination [methotrexate, vinblastine, doxorubicin, and cisplatin (mvac)], the overall response rate (or) was only 12% in the cisplatin arm, with only 4 of 122 patients (3.3%) remaining alive at 3 years of follow-up 4 . Similar results were observed in phase ii trials with carboplatin [or: 18%; median duration of survival (mds): 16 months] 5 . In a phase iii trial examining the role of lobaplatin, 2 of 17 patients (12%) achieved a partial response (pr), but the study was terminated because of high toxicity rates 6 . Other drugs investigated in phase ii trials have manifested variable activity against advanced urothelial cancer: oral piritrexim (or: 23%; mds: 22 weeks) 7 , trimetrexate (or: 17%; mds not reported) 8 , and docetaxel (or: 13%; mds: 9 months) 9 . However, some improved results were obtained with other single agents such as paclitaxel and gemcitabine 10,11 . In a phase ii trial of 26 patients with advanced bc treated with paclitaxel, the or was 42%, and the mds, 8.4 months 10 . Similarly, in a phase ii trial of gemcitabine in 40 patients, an or of 28% was reported, with a mds of 54 weeks 11 . ABSTRACTUrothelial cancer of the bladder is the 4th most common malignancy in American men and the 9th most common in women. Although it is a chemosensitive disease, advanced bladder cancer seems to have reached a plateau with regard to median survival of patients. Standard first-line therapy remains gemcitabine plus cisplatin (gc) or methotrexate, vinblastine, doxorubicin, and cisplatin (mvac). In patients deemed unfit to receive cisplatin, gemcitabine plus carboplatin or gemcitabine plus paclitaxel can be considered. To date, no standard therapy has been established for patients who recur or are refractory to first-line therapy. Second-line vinflunine, by way of superiority over best supportive care, has shown promise in a phase iii trial. Cisplatin-based therapy (mvac or gc) can also be offered to patients previously treated with cisplatin, especially if they responded previously and are considered platinum-sensitive. Novel targeted therapies are sorely needed to further improve the delivery and efficacy of chemotherapy.

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“…For previous chemotherapy, 18 patients received the GC regimen as the first-line and the M-VAC regimen as the second-line treatments, and three patients received M-VAC as the first-line and GC as the second-line treatments. The median treatment-free interval was 3.5 months (range [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The response rate including complete remission (CR) and PR of the previous two regimens was 38.1%.…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…For GC and M-VAC chemotherapy, the specific dose and schedules were the same as in previous reports. 8 For GC chemotherapy, gemcitabine was given at a dose of 1000 mg/m 2 on days 1, 8 and 15, and cisplatin was given at a dose of 70 mg/m 2 on days 2. For M-VAC chemotherapy, the patients received methotrexate 30 mg/m 2 on days 1, 15 and 22; vinblastine 3 mg/m 2 on days 2, 15 and 22; doxorubicin 30 mg/m 2 on day 2; and cisplatin 70 mg/m 2 on day 2.…”

Section: Patientsmentioning

confidence: 99%

“…In a previous study, we showed that M-VAC is a reasonable choice as a second-line regimen in patients who received GC as a first-line regimen. 8 Clinicians often encounter patients who failed in the second-line regimen and still strongly want further treatment with good physical eligibility. To our knowledge, there is no study on optional chemotherapy as a third-line regimen for patients with metastatic urothelial carcinoma.…”

Section: Introductionmentioning

confidence: 99%

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Paclitaxel and cisplatin chemotherapy for metastatic urothelial carcinoma after failure of two courses of platinum‐based regimens

et al. 2011

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Objectives:We investigated the outcomes of paclitaxel and cisplatin chemotherapy as an optional regimen for patients with metastatic urothelial carcinoma after failure of two consecutive platinum-based regimens. Methods: We retrospectively analyzed the data of 21 patients who had evidence of disease progression after two consecutive platinum-based regimens, gemcitabine and cisplatin (GC course), and methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC course) as first-line and second-line treatments. As third-line chemotherapy, patients received paclitaxel (175 mg/m 2 ) and cisplatin (70 mg/m 2 ) every 3 weeks until disease progression. Results: Complete remission occurred in one patient (4.8%), partial remission occurred in three patients (14.3%) and stable disease occurred in five patients (23.8%). The overall response rate was 19.0% and the overall disease control rate, including stable disease, was 42.9%. The median progression-free survival (PFS) was 3 months (95% CI 3.0-5.0). The median overall survival was 9 months (95% CI 7.0-15.0). Grade 3 to 4 neutropenia appeared in 85.7% of patients. No life-threatening complications were observed. Conclusions: Paclitaxel and cisplatin chemotherapy could be an optional regimen for patients with metastatic urothelial carcinoma after the failure of two consecutive standard platinum-based regimens.

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Methotrexate, vinblastine, doxorubicin and cisplatin combination regimen as salvage chemotherapy for patients with advanced or metastatic transitional cell carcinoma after failure of gemcitabine and cisplatin chemotherapy

Cited by 49 publications

References 29 publications

The combination of paclitaxel and carboplatin as second-line chemotherapy can be a preferred regimen for patients with urothelial carcinoma after the failure of gemcitabine and cisplatin chemotherapy

The combination of paclitaxel and carboplatin as second-line chemotherapy can be a preferred regimen for patients with urothelial carcinoma after the failure of gemcitabine and cisplatin chemotherapy

First- and Second-Line Therapy for Metastatic Urothelial Carcinoma of the Bladder

Paclitaxel and cisplatin chemotherapy for metastatic urothelial carcinoma after failure of two courses of platinum‐based regimens

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