1000/1000
Hot
Most Recent
Urothelial carcinoma (UC), the sixth most common cancer in Western countries, includes upper tract urothelial carcinoma (UTUC) and bladder carcinoma (BC) as the most common cancers among UCs (90–95%). BC is the most common cancer and can be a highly heterogeneous disease, including both non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) forms with different oncologic outcomes. Approximately 80% of new BC diagnoses are classified as NMIBC after the initial transurethral resection of the bladder tumor (TURBt).
Author, Year | Patients Number | Study Design | Treatment | Regimen | Effects of Treatment | Main Findings |
---|---|---|---|---|---|---|
Chevuru et al., 2023 [25] | 97 | Retrospective | Gemcitabine Docetaxel |
Induction +/− maintenance | Gemcitabine: inhibition of DNA synthesis Docetaxel: inhibition of cell division |
12, 24, and 60 months RFS 57%, 44%, and 24% (12, 24, and 60 months HG-RFS 60%, 50%, and 30%, respectively); BCG unresponsive: 12, 24, and 60 months RFS 67%, 50%, and 28%; CIS-only: 1-, 2-, and 5-year RFS 48%, 38%, and 22%, papillary only: 1-, 2-, and 5-year RFS 64%, 49%, and 25% (p = 0.3); 12, 24, and 60 months RC-free survival 89%, 86%, and 75% |
Hurle et al., 2020 [26] |
36 | Open-label, single-arm | Gemcitabine | Induction +/− maintenance | Gemcitabine: inhibition of DNA synthesis | 12 and 24 months DFS 44.44% (95% CI 28.02–59.64%) and 31.66% (95% CI 16.97–47.43%); 12 and 24 months PFS 80.13% (95% CI: 62.78–90.00%) and 69.55% (95% CI: 50.33% 82.52%), 24 months CSS 80.68% (95% CI 61.49–90.96%), 24 months OS 77.9% (95% CI 58.78–88.92%) |
Steinberg et al., 2020 [27] | 276 | Retrospective | Gemcitabine Docetaxel |
Induction +/− maintenance | Gemcitabine: inhibition DNA synthesis Docetaxel: inhibition of cell division |
1 and 2 years RFS 60% and 46% (43% if CIS present); HG 1 and 2 years RFS 65% and 52% (50% if CIS present) |
DeCastro et al., 2020 [28] | 18 | Phase I trial | Cabazitaxel Gemcitabin Cisplatin |
Induction +/− maintenance (cabazitaxel + gemcitabine) | Cabazitaxel: inhibition of cell division Gemcitabine: inhibition of DNA synthesis Cisplatin: inhibition of DNA replication and transcription |
CR rate: 89%; PR: 94% (negative biopsy but positive cytology). One and two years RFS 0.83 (range 0.57 to 0.94) and 0.64 (0.32 to 0.84), median 27 months. One- and two-years RC-free survival 0.94 (0.67 to 0.99) and 0.81 (0.52 to 0.94) |
Milbar et al., 2017 [29] | 33 (22 BCG unresponsive/relapsing) | Retrospective | Gemcitabine Docetaxel |
Induction +/− maintenance | Gemcitabine: inhibition DNA synthesis Docetaxel: inhibition of cell division |
1 and 2 years DFS38% and 24%. One and two years HG-RFS 49% and 34%. |
Dalbagni et al., 2017 [30] | 19 | Single-arm, phase I/II trial | Gemcitabine Everolimus (oral) |
Gemcitabine induction + everolimus maintenance | Gemcitabine: inhibition of DNA synthesis Everolimus: mTOR inhibition |
3, 6, and 9, 12 months RFS 58% (95% CI 33–76%), 27% (95% CI 9–49%) and 20% (95% CI 5–42%) |
Robins et al., 2017 [31] | 22 | Single-arm, open-label, phase II trial | Nab-paclitaxel | Induction +/− maintenance | Nab-paclitaxel: inhibition of cell division | Overall CR 36%, non-CIS CR 63, CIS CR 25%. One and three-year RFS 32% and 18% (no CIS CR 40%, CIS CR 10%), |
Cockerill et al., 2016 [32] | 27 | Retrospective | Gemcitabine MMC |
Induction, no standardized maintenance | Gemcitabine: inhibition of DNA synthesis MMC: inhibition of DNA functions. |
63% recurrence rate, median RFS 15.2 months (range 1.7–32). RFS 37% (median follow-up 22 months) |
Steinberg et al., 2015 [33] | 45 | Retrospective | Gemcitabine Docetaxel |
Induction +/− maintenance | Gemcitabine: inhibition of DNA synthesis Docetaxel: inhibition of cell division |
Treatment success (no recurrence + no cystectomy) 66% at 12 weeks, 54% at 1 year, 34% at 2 years; median time to failure 3.1 months (range 2.2–25.9) |
Lightfoot et al., 2014 [34] | 52 (10 BCG naive) | Retrospective | Gemcitabine MMC |
Induction +/− maintenance | Gemcitabine: inhibition of DNA synthesis MMC: inhibition of DNA functions. |
CR 68%, 1- and 2-year RFS, 48%, and 38% |
McKiernan et al., 2014 [35] | 28 | Single-arm, phase II trial |
Nab-paclitaxel | Induction +/− maintenance | Nab-paclitaxel: inhibition of cell division | 35.7% CR, 1 and 2-year RFS 35.7% and RFS 30.6%. 12, 24, and 36 months CFS 74%, 74%, and 55% |
Barlow et al., 2013 [36] | 54 | Retrospective | Docetaxel | Induction +/− maintenance | Docetaxel: inhibition of cell division | 59% CR (cystoscopy with biopsy + cytology); 1- and 3-year RFS 40% and 25%; 31% RC rate |
Skinner et al., 2013 [37] | 58 | Single-arm, open-label, phase II trial | Gemcitabine | Induction +/− maintenance | Gemcitabine: inhibition of DNA synthesis | 3 months CR (negative cystoscopy, urinary cytology +/− biopsy) 47%. Median RFS 6.1 months (95% CI 16–43), 21% at 24 months. Progression/RC rate 36%. |
Sternberg et al., 2013 [38] | 69 | Retrospective | Gemcitabine | Induction | Gemcitabine: inhibition of DNA synthesis | 5 years progression rate 19% for BCG-refractory pts, 22% for pts with other types of BCG failure (HR 1.09, 95% CI 0.34–3.50). CR (negative cystoscopy and cytology) in 27 pts, PR (negative cystoscopy and positive cytology in 19 with), NR (positive cystoscopy) 20 pts. Subsequent RC in 20 pts |
Steinberg et al., 2011 [39] | 90 | Single-arm, pivotal phase III open-label study | Valrubicin | Induction | Valrubicin: inhibition of DNA and RNA synthesis | CR in 18 pts at 3 and 6 months (negative cytology, cystoscopy, and biopsy), NR 64 pts |
McKiernan et al., 2011 [40] | 18 | Phase I trial | Nab-paclitaxel | Induction | Nab-paclitaxel: inhibition of cell division | CR in 5 patients (28%), 13 NR (stage progression in 1) |
Bassi et al., 2011 [41] | 16 | Single-arm, open-label, phase I trial | Paclitaxel-hyaluronic acid | Induction | Paclitaxel: inhibition of cell division | 6 NR (40%), 9 disease-free pts (60%) |
Di Lorenzo et al., 2010 [42] | 80 | Multicentric, phase II trial, randomized | Gemcitabine vs. BCG | Induction + maintenance for both arms | Gemcitabine: inhibition of DNA synthesis BCG: stimulating cellular and humoral immune response |
2-year RFS 19% for Gem (95% CI, 5–39), 3% for BCG (95% CI, 0–21; HR, 0.15; 95% CI, 0.1–0.3.008). Progression rate 33% for Gem, 37.5% for BCG |
Perdonà et al., 2010 [43] | 20 | Single-arm, phase II trial | Gemcitabine | Induction + maintenance | Gemcitabine: inhibition of DNA synthesis | 3 months CR at the first 75%; 55% recurrence rate (11 of 20 pts); 45% progression rate (5 of 11 pts) |
Laudano et al., 2010 [44] | 18 | Single-arm, phase I trial | Docetaxel | Induction | Docetaxel: inhibition of cell division | 22% CR, 17% PR (NMIBC recurrence requiring TURBT with no further treatment), 61% NR (RC or further pharmacologic therapy). PFS 89%. |
Addeo et al., 2010 [45] | 109 | Phase III trial randomized | Gemcitabine vs. MMC | Induction +/− maintenance for both arms | Gemcitabine: inhibition of DNA synthesis MMC: inhibition of DNA functions. |
RFS in gemcitabine arm, 72% (39 of 54 pts), in MMC arm 61% (33 of 55 pts). Stage progression in 10 pts in the MMC arm and 6 in the gem arm |
Ignatoff et al., 2009 [46] | 38 | Multicentric, single-arm, phase II trial | AD32 (doxorubicin analog with limited systemic exposure) |
Induction | AD32: inhibition of DNA functions and induction of apoptosis | CR 42.9% (90% CI: 24.5%, 62.8%), CIS CR 23.8% (90% CI: 9.9%, 43.7%). 12 and 24 RFS months 20% (90% CI: 7.8–36.1%) and 15% (CI, 4.9%, 30.2%),12 and 24 CIS RFS 80% (90% CI, 31.4%, 95.8%) if previous CR. PFS 22.4 months, CIS PFS 8.7 months |
Mohanty et al., 2008 [47] | 35 | Single-arm, non-randomized, phase I trial |
Gemcitabine | Induction | Gemcitabine: inhibition of DNA synthesis | At 18 months follow-up 21 disease free pts (60%), 11 pts (31.4%) with superficial recurrences, 3 (8.75%) with MIBC. Average RFS 12 months, average time to progression 16 months. |
Gunelli et al., 2007 [48] | 40 | Single-arm, phase II trial |
Gemcitabine | Induction | Gemcitabine: inhibition of DNA synthesis | 95% (38 of 40 pts) CR at 6 months (cystoscopy + cytology); overall event-free survival rate 80% at 1 year and 66% at 2.5 years. At a median follow-up of 28 months, 35% relapse rate (NMIBC). RC in 2 pts |
Dalbagni et al., 2006 [49] | 30 | Single-arm, phase II trial | Gemcitabine | Induction | Gemcitabine: inhibition of DNA synthesis | 50% CR; median RFS 3.6 months (95% CI, 2.9 to 11.0 months); 21% 1-year RFS in pevious CR (95% CI, 0% to 43%). RC rate 37% |
McKiernan et al., 2006 [50] | 18 | Single-arm, phase I trial | Docetaxel | Induction | Docetaxel: inhibition of cell division | CR in 56% (10 pts) |
Bartoletti et al., 2005 [51] | 40 BCG refractory (total population 116) | Multicentric, single-arm, phase II trial | Gemcitabine | Induction | Gemcitabine: inhibition of DNA synthesis | Recurrence rate 32.5%, relapse in 6 (25%) of 24 intermediate-risk BCG refractory pts and 7 (43.7%) of 16 BCG refractory high-risk pts |
Bassi et al., 2005 [52] | 9 | Single-arm, phase I trial | Gemcitabine | Induction +/− maintenance | Gemcitabine: inhibition of DNA synthesis | CR in 4/9 pts |
Dalbagni et al., 2002 [53] | 14 | Single-arm, phase I trial | Gemcitabine | Induction (dose levels 500 mg, 1.000 mg, 1.500 mg, and 2.000 mg. | Gemcitabine: inhibition DNA synthesis | CR (defined as a negative posttreatment cystoscopy with biopsy of the urothelium + negative cytology) in 7, failure in 11 (negative bladder biopsy + persistent positive cytology), RC rate 1/11 pts |