Neoadjuvant chemotherapy with DD-MVAC and bevacizumab in high-risk urothelial cancer: Results from a phase II trial at the M. D. Anderson Cancer Center.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 261-261 ◽  
Author(s):  
Arlene O. Siefker-Radtke ◽  
Ashish M. Kamat ◽  
Paul G. Corn ◽  
Surena F. Matin ◽  
H. Barton Grossman ◽  
...  
Keyword(s):  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Urothelial Cancer ◽  
Cancer Center ◽  
Upper Tract ◽  
Metastatic Urothelial Cancer ◽  
Eligibility Requirements ◽  
Grade 3

261 Background: DD-MVAC has shown an improved 5-year survival in metastatic urothelial cancer; however, there is no prospective data on its use in the neoadjuvant setting. Previous work suggested that over-expression of VEGF was associated with a high risk of relapse in our neoadjuvant patients, leading to the hypothesis that combining a VEGFR inhibitor with chemotherapy may improve patient outcomes. Methods: Between 8/07 and 12/10, 60 patients with urothelial carcinoma of the bladder or upper tract tumor were enrolled on a prospective phase II clinical trial. Eligibility requirements included at least one of the following: 3-D mass on EUA (cT3b disease), LVI, hydronephrosis, micropapillary features, tumor in a diverticula, and for upper tract tumors a high grade tumor or radiographically measurable sessile mass. The primary endpoint was pathologic down-staging to <=pT1N0M0. Results: Forty-four patients with bladder/urethral tumors and 16 patients with upper tract tumors were enrolled. Pathologic down-staging to <= pT1N0M0 occurred in 53% of patients overall (bladder/urethra 45%, upper tract 75%), and to <= pT0N0M0 in 38% overall (bladder/urethra 39%, upper tract 38%). At a median follow-up of 21 months, the 2-year OS and DSS was 78% and 85%, respectively (bladder 2-yr OS and DSS 75%, 82%; upper tract 93%, 93%). The median OS and DSS have not yet been reached. The most common grade 3 or greater toxicity was neutropenia in 27% of patients, followed by fatigue in 10%. The following grade 3 toxicities were observed in < 10% of patients: mucositis, DVT/PE, hypertension, nausea/vomiting, thrombocytopenia. One patient experienced cardiac ischemia. Conclusions: Neoadjuvant chemotherapy leads to pathologic down-staging in 45% of patients with bladder cancer. DD-MVAC appears an acceptable alternative to traditional M-VAC in the neoadjuvant setting. Although bevacizumab did not impact down-staging based upon historical expectations, determining the effect on recurrence requires longer follow-up.

Neoadjuvant chemotherapy with DD-MVAC and bevacizumab in high-risk urothelial cancer: Results from a phase II trial at the University of Texas M. D. Anderson Cancer Center.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4523-4523 ◽  
Author(s):  
Arlene O. Siefker-Radtke ◽  
Ashish M. Kamat ◽  
Paul G. Corn ◽  
Surena F. Matin ◽  
H. Barton Grossman ◽  
...  
Keyword(s):  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Urothelial Cancer ◽  
Cancer Center ◽  
Upper Tract ◽  
Metastatic Urothelial Cancer ◽  
Eligibility Requirements ◽  
Grade 3

4523 Background: DD-MVAC has shown an improved 5-year survival in metastatic urothelial cancer; however, there is no prospective data on its use in the neoadjuvant setting. Previous work suggested that over-expression of VEGF was associated with a high risk of relapse in our neoadjuvant patients, leading to the hypothesis that combining a VEGFR inhibitor with chemotherapy may improve patient outcomes. Methods: Between 8/07 and 12/10, 60 patients with urothelial carcinoma of the bladder or upper tract tumor were enrolled on a prospective phase II clinical trial. Eligibility requirements included at least one of the following: 3-D mass on EUA (cT3b disease), LVI, hydronephrosis, micropapillary features, tumor in a diverticula, and for upper tract tumors a high grade tumor or radiographically measurable sessile mass. The primary endpoint was pathologic down-staging to <=pT1N0M0. Results: Forty-four patients with bladder/urethral tumors and 16 patients with upper tract tumors were enrolled. Pathologic down-staging to <= pT1N0M0 occurred in 53% of patients overall (bladder/urethra 45%, upper tract 75%), and to <= pT0N0M0 in 38% overall (bladder/urethra 39%, upper tract 38%). At a median follow-up of 26 months, the 2-year OS and DSS was 78% and 82%, respectively (bladder 2-yr OS and DSS 75%, 78%; upper tract 93%, 93%). The median OS and DSS have not yet been reached. The most common grade 3 or greater toxicity was neutropenia in 27% of patients, followed by fatigue in 10%. The following grade 3 toxicities were observed in < 10% of patients: mucositis, DVT/PE, hypertension, nausea/vomiting, thrombocytopenia. One patient experienced cardiac ischemia. Conclusions: Neoadjuvant chemotherapy leads to pathologic down-staging in 45% of patients with bladder cancer. DD-MVAC appears an acceptable alternative to traditional M-VAC in the neoadjuvant setting. Although bevacizumab did not impact down-staging based upon historical expectations, determining the effect on recurrence requires longer follow-up.

scholarly journals Phase II Trial of Cetuximab With or Without Paclitaxel in Patients With Advanced Urothelial Tract Carcinoma

2012 ◽  
Vol 30 (28) ◽  
pp. 3545-3551 ◽  
Author(s):  
Yu-Ning Wong ◽  
Samuel Litwin ◽  
David Vaughn ◽  
Seth Cohen ◽  
Elizabeth R. Plimack ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Metastatic Setting ◽  
Previously Treated ◽  
Grade 3

Purpose The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer. Patients and Methods Patients with metastatic urothelial cancer who received one line of chemotherapy in the perioperative or metastatic setting were randomly assigned to 4-week cycles of cetuximab 250 mg/m2 with or without paclitaxel 80 mg/m2 per week. We used early progression as an indicator of futility. Either arm would close if seven of the initial 15 patients in that arm progressed at the first disease evaluation at 8 weeks. Results We enrolled 39 evaluable patients. The single-agent cetuximab arm closed after nine of the first 11 patients progressed by 8 weeks. The combination arm completed the full accrual of 28 patients, of whom 22 patients (78.5%) had visceral disease. Twelve of 28 patients had progression-free survival greater than 16 weeks. The overall response rate was 25% (95% CI, 11% to 45%; three complete responses and four partial responses). The median progression-free survival was 16.4 weeks (95% CI, 12 to 25.1 weeks), and the median overall survival was 42 weeks (95% CI, 30.4 to 78 weeks). Treatment-related grade 3 and 4 adverse events that occurred in at least two patients were rash (six cases), fatigue (five cases), and low magnesium (three cases). Conclusion Although it had limited activity as a single agent, cetuximab appears to augment the antitumor activity of paclitaxel in previously treated urothelial cancers. The cetuximab and paclitaxel combination merits additional study to establish its role in the treatment of urothelial cancers.

scholarly journals Incidence and Predictors of Secondary Upper Tract Urothelial Cancer in Patients with High-Risk Non-Muscle Invasive Urinary Bladder Cancer and its Impact on Imaging Surveillance: A Retrospective Analysis with 1501 Patients

2021 ◽  
Vol 2 (3) ◽  
pp. 151-157
Author(s):  
Ebrahim Elsaeed Abouelenein ◽  
Mohamed Elawdy ◽  
Diaa-Eldin Taha ◽  
Yasser Osman ◽  
Bedeir Ali-El Dein ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Urothelial Cancer ◽  
Multivariable Analysis ◽  
Bladder Tumors ◽  
Upper Tract ◽  
Upper Tract Urothelial Cancer ◽  
Imaging Surveillance ◽  
Muscle Invasive

Objectives: We aimed to study the incidence and predictors of upper tract urothelial cancer (UTUC) in patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC). Methods: Patients who had HR-NMIBC were reviewed to identify those who subsequently developed UTUC. Complete transurethral resection was performed, and biopsies were collected for histopathology followed by intravesical chemoimmunotherapy. Patients were screened annually by computed tomography (CT) for UTUC. Results: Data for 1501 patients were reviewed. UTUC developed in 59 (4%) after a median of 20 months after HR-NMIBC. Most patients were symptomatic, but UTUC was discovered on routine follow-up imaging in 28%. On bivariate analysis, only multiple bladder tumors and the number of bladder recurrences were predictors for UTUC (P = 0.01 and P = 0.008, respectively). Multiple bladder tumors and ≥ 3 bladder recurrences remained significant on multivariable analysis. Conclusion: UTUC after HR-NMIBC is uncommon (4%). Despite routine follow-up CT imaging, recurrence was detected due to symptoms in most patients, and based on imaging only in 28%. Imaging surveillance can be prioritized in patients with multiple bladder tumors and those with ≥ 3 bladder recurrences. For the other patients, the benefit of imaging surveillance has to be weighed against the risks.

A Phase II Study of Myeloablative I-131-Anti CD-20 (Tositumomab) Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Adults ≥60 Years of Age with High-Risk Relapsed or Refractory B-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 487-487 ◽  
Author(s):  
Ajay K. Gopal ◽  
Joseph G. Rajendran ◽  
Ted A. Gooley ◽  
John M. Pagel ◽  
Darrell R. Fisher ◽  
...  
Keyword(s):  
Older Adults ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Transplantation ◽  
Phase Ii ◽  
High Dose ◽  
Grade 3

Abstract The majority of patients with relapsed or refractory B-cell, non-Hodgkin’s lymphoma (NHL) are over 60 years of age, yet many are denied potentially curative high-dose regimens due to concerns of excessive toxicity with stem cell transplantation in this age group. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be ideal for older adults requiring high-dose therapy. We have treated 24 patients with relapsed or refractory B-cell NHL aged ≥60 years using high-dose I-131-tositumomab (GlaxoSmithKline) and ASCT on a phase II trial. Patients were required to have a performance status of 0–1, acceptable organ function, ≥2x106 CD34+ cells/kg collected, and &lt;20 Gy prior radiation to critical organs. Patients with splenomegaly or tumor bulk over 500cc were required to undergo further cytoreduction or splenectomy in order to optimize biodistribution of the radiolabeled antibody. Patients without evidence of disease at the time of therapy were excluded. All pts underwent outpatient dosimetry using tositumomab (1.7 mg/kg) labeled with 5–10mCi I-131 followed by serial quantitative gamma camera imaging and patient and organ-specific dosimetry. Patients then received individualized infusions of I-131-tositumomab (1.7 mg/kg) to deliver 25–27Gy to the critical normal organ receiving the highest radiation dose followed by ASCT. Between 12/1/99 and 4/29/05 24 pts were enrolled on this study. Baseline characteristics included: median age at ASCT = 64 yrs (range 60–76 yrs), male = 15/24, median number of prior regimens = 4 (range 2–14), chemoresistant disease (defined as &lt; a partial response to the most recent regimen) = 13/24, Stage III/IV=100%, &gt;1 extranodal site = 21%, elevated LDH at treatment = 46%, IPI score at transplant 3–5 = 46%, Histology: diffuse large B-cell (DLBCL)=9 pts (with 4/9 transformed from follicular lymphoma [FL]), mantle cell (MCL)=8 pts, FL=6 pts, and marginal zone (MZL) 1 pt. The median I-131 activity administered was 525 mCi (range 328–1154 mCi) with dose limiting organs being lung, liver, and kidney in 12, 8, and 4 patients, respectively. The therapy was well tolerated with no treatment-related deaths, and no grade 3–4 Bearman toxicity. NCI CTC non-hematopoeitic toxicities by day 100 included: Grade 4=2/24 and Grade 3=17/24. The median time after ASCT for recovery of platelets &gt; 20K and neutrophils &gt;500 was 10 and 15 days, respectively. Sixteen of 24 pts remain alive (67%) and 10 (42%) are alive and progression-free with a median follow up from ASCT of 2.2 yrs (range 1 mo.–4.9 yrs.) for survivors. The estimated 3-year overall and progression-free survival are 56% and 37%, respectively. Surviving patients include 6/8 with MCL, 5/7 with FL/MZL, and 5/9 with DLBCL as well as 9/13 with chemoresistant disease. Myeloablative I-131-tositumomab with ASCT is a well-tolerated and effective transplant option for older adults with high-risk, relapsed B-NHL, though longer follow-up and additional pts will be needed to confirm the reproducibility and durability of these findings.

Phase II Study of Sunitinib in Patients With Metastatic Urothelial Cancer

2010 ◽  
Vol 28 (8) ◽  
pp. 1373-1379 ◽  
Author(s):  
David J. Gallagher ◽  
Matthew I. Milowsky ◽  
Scott R. Gerst ◽  
Nicole Ishill ◽  
Jamie Riches ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Tumor Regression ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3 ◽  
Endothelial Growth Factor

Purpose No standard therapy exists for metastatic urothelial cancer (UC) that has progressed after initial chemotherapy. This trial was designed to assess the efficacy and tolerability of sunitinib in patients with advanced, previously treated UC. Patients and Methods In this phase II trial, 77 patients received sunitinib between September 2006 and January 2009 on one of two schedules (50 mg per day for 4 weeks on and 2 weeks off [cohort A], 37.5 mg per day continuously [cohort B]), using a Simon 2 stage design in each cohort separately. Results A partial response was seen in three of 45 patients (95% CI, 1% to 18%) in cohort A, and in one of 32 patients (95% CI, 0% to 16%) in cohort B. Clinical regression or stable disease was achieved in 33 of 77 patients (43%). Tumor regression lasted between 0.6 and 23.4 months with 29% of patients achieving response lasting longer than 3 months. The progression-free survival (2.4 v 2.3 months; P = .4) and overall survival (7.1 v 6.0 months; P = .4) were similar in both cohorts. There was one treatment-related death, and 47 patients (33 cohort A, 24 cohort B) experienced grade 3 or 4 toxicity. Conclusion Sunitinib did not achieve the predetermined threshold of ≥ 20% activity defined by Response Evaluation Criteria in Solid Tumors. However, antitumor responses were observed, identifying the vascular endothelial growth factor axis as a viable pathway for UC treatment. The reported clinical benefit in previously treated patients warrants further investigation in a disease for which there is no US Food and Drug Administration–approved treatment.

Final results from a phase II trial of systemic chemotherapy in a small cell urothelial cancer: Evidence supporting neoadjuvant chemotherapy from the M.D. Anderson Cancer Center

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5083-5083
Author(s):  
A. O. Siefker-Radtke ◽  
A. M. Kamat ◽  
H. Grossman ◽  
D. L. Williams ◽  
C. P. Dinney ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Urothelial Cancer ◽  
Cranial Irradiation ◽  
Colon Resection ◽  
Prophylactic Cranial Irradiation ◽  
Small Cell ◽  
Cancer Center ◽  
Maximal Response ◽  
Additional Support

5083 Background: Previously reported retrospective data supported a potential role for neoadjuvant chemotherapy in small cell urothelial cancer (SCUC). We now report final results from a phase II clinical trial in SCUC. Methods: Since 2001, 30 patients with biopsy proven SCUC received alternating doublet chemotherapy with Ifosfamide + Doxorubicin, and Etoposide + Cisplatin. Patients with surgically resectable disease (<=cT4aN0M0) received a total of 4 cycles followed by cystectomy, while those with unresectable disease (>=cT4b, N+, or M+) received 2 cycles beyond maximal response. Results: Neoadjuvant chemotherapy was given in 18 patients (cT2:14, cT3:4), while 12 patients were treated for metastatic SCUC. For those receiving neoadjuvant therapy, the median OS is 58 months, with a 5-year survival of 48%; 8 remain alive and NED beyond 2.5 years. There have been only 5 deaths for the neoadjuvant group (3 SCUC, 1 post-op infection, 1 AML). For those with metastatic disease, the median OS is 14 months. Two were rendered resectable with chemotherapy (cT4b:1,N+:1); 1 died of recurrent SCUC, while the other is currently undergoing therapy for TCC of the ureter. Brain metastases developed in 7 patients (cT3b:2, initial M+:5). Chemotherapy has been well-tolerated with only 2 G4 toxicities (catheter infection and neutropenia). The most frequent G3 toxicities include transfusion (10), neutropenic fever (7), infection (5), and vomiting (3). There was only one post-surgical death; a case of sepsis in a patient with diverticulitis and abscess requiring sigmoid colon resection. Conclusions: These prospective results, which are consistent with our previously reported retrospective review, provide additional support for 4 cycles of neoadjuvant chemotherapy in the setting of SCUC. Unfortunately, once metastases are present, the prognosis remains poor with few long-term survivors. These results may also predict a patient subset for which prophylactic cranial irradiation may be potentially beneficial. No significant financial relationships to disclose.

Phase II trial of pazopanib and weekly paclitaxel in metastatic urothelial cancer (UC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 299-299 ◽  
Author(s):  
Sandy Srinivas ◽  
Sujata Narayanan ◽  
Lauren Christine Harshman ◽  
Anthony P. Lam ◽  
Ulka N. Vaishampayan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Weekly Paclitaxel ◽  
Ecog Performance Status ◽  
Metastatic Urothelial Cancer ◽  
Grade 3

299 Background: Currently, there are no standard treatments for relapsed or refractory urothelial carcinoma (UC). Discouraging results have been achieved in trials evaluating drugs as single agents or in combination regimens. Paclitaxel has activity when used alone and in combination in urothelial cancer, and pazopanib is active in solid tumors secondary to its potent anti-angiogenic effect. We report the results of an ongoing multicenter phase II study evaluating the combination of paclitaxel with pazopanib in refractory UC. Methods: Patients (pts) eligible for the study have histologically confirmed UC, with relapse after receiving up to 2 chemotherapeutic regimens. Pazopanib (800 mg) is administered daily, with weekly paclitaxel (80mg/m2) for 3 weeks in a 28 day cycle. Treatment is continued until disease progression or unacceptable toxicity. Primary endpoint of the study is the response-rate (RR) based on RECIST criteria. Secondary endpoints include safety, and progression free-survival (PFS). For designing the study, Simon’s two-stage method was applied, and 9 pts were recruited in the first stage. After having ≥1 response in the first group, a full enrollment of 32 pts has been initiated. Results: 25 pts were enrolled from April 2010 to September 2013. Their median age was 67 years (47-89), with a median ECOG performance status of 1 (0-2). 10 pts (40%) had UC of the upper urinary tract and 15 had primary bladder/ureter tumors. All pts had multiple metastatic sites, including 11 (44%) with liver metastases. Median number of prior cytotoxic regimens was 2, and 50% were considered cisplatin responsive. Based on RECIST (v1.1) criteria,13 pts (52%) had partial response (PR), 5 (20%) had stable disease (SD), and 2 (8%) had complete response (CR) (80% clinical benefit). The side effects included grade 3 hypertension (n=2), grade 3 fatigue (n=4), grade 3 thrombosis (n=2) and grade 4 neutropenia (n=2). 14 pts required growth factor support. Conclusions: Our phase II study combining paclitaxel and pazopanib demonstratedsignificant anti-tumor activity of combining paclitaxel in relapsed/refractory UC. This combination is safe, and is worthy of evaluation in larger studies. Clinical trial information: 1108055.

Preliminary Results of Phase II Trial of Clofarabine with Parenteral Busulfan Followed by Allogeneic Related or Unrelated Donor Transplantation for the Treatment of Hematologic Malignancies and Diseases.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4954-4954 ◽  
Author(s):  
Edward D. Agura ◽  
R. Brian Berryman ◽  
Joseph W. Fay ◽  
Luis A. Pineiro ◽  
Estil A. Vance ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Response To Therapy ◽  
Unrelated Donor ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Full Intensity

Abstract Background: Nonablative transplant regimens are useful to treat patients who are elderly or too ill to undergo a full-intensity ablative allogeneic transplant regimen. However, this approach is limited by a higher relapse rate in some situations. We developed a novel conditioning regimen using the nucleoside analogue clofarabine (CLO) with busulfan (BU) to treat elderly patients with acute leukemia or high risk MDS who are not in remission or are at high risk of relapse. Methods: Five patients were enrolled on this single institution; phase II, IRB-approved trial, so far. The diagnoses at the time of transplant were two with AML, one with ALL, and two with MDS. All patients received CLO 40mg/m2/day iv on d-7 through d-4 followed by BU 3.2 mg/m2/day iv on d-3 and -2, followed by infusion of HLA matched related or unrelated donor PBSC on day 0. GVHD prophylaxis consisted of oral FK506 and MTX 5mg/m2 iv d + 1, +3 and +6. BU and CLO pharmacokinetic samples were collected on all patients for later PK analysis. Results: Primary endpoints included toxicity and response to therapy. There were no cases of hepatic, cardiac, or renal toxicity attributed to the conditioning regimen by d+30. Acute toxicities included hand/foot syndrome, n=2 (one grade 1, and one grade 3 by CTCAE v 3.0); fluid retention, n=3 (2 grade 1 and 1 grade 2). All patients had hematologic nadirs lasting 12 to 15 days. GCSF was used in 4 of 5 subjects. 5 of 5 patients achieved allogeneic engraftment with myeloid cells by day +30. Response to therapy was documented in 4 patients by d+30, one is not yet evaluated. One (1) patient relapsed by d+62. 3 of 4 remain in remission with follow up ranging from 60 to 117 days. Conclusions: CLO + BU is a novel allogeneic conditioning regimen that seems to be well tolerated by the small number of subjects treated so far at our institution. The follow up is not long enough to conclude more at this time. The study continues to accrue patients and will be updated at the meeting.

Rate of durable complete remission (CR) using two sequential, dose-dense regimens of cisplatin, gemcitabine, paclitaxel (CGP) followed by m-VAC in patients with metastatic urothelial cancer (mUC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15502-e15502
Author(s):  
Matteo Brighenti ◽  
Stefano Panni ◽  
Bruno Perrucci ◽  
Mariangela Maltese ◽  
Wanda Liguigli ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Supportive Therapy ◽  
Complete Response ◽  
Improve Response Rate ◽  
Metastatic Urothelial Cancer ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
Dose Dense ◽  
Metastatic Sites

e15502 Background: mUC is a chemotherapy sensitive tumor. Currently, CGP and MVAC are the most active regimens in this setting. According to Norton and Simon hypothesis, the administration of two sequential non cross-resistant, dose-dense chemotherapy regimens may target different cancer cells, avoid drug resistance, improve response rate and CR. Methods: Patients with histological diagnosis of mUC, PS 0–2 (ECOG), adequate organ function and no previous systemic regimens were treated with 4 cycles of CGP dose-dense (Gemcitabine 1000 mg/m2 d 1, Paclitaxel 140 mg/m2 d 1, Cisplatin 70 mg/m2 d 2 plus PegFilgrastim 6 mg on day 3, every 2 weeks) followed by 4 cycles of M-VAC (Methotrexate 30 mg/m2 d 1,Vinblastine 3 mg/m2 d 2, Doxorubicin 30 mg/m2 d 2, Cisplatin 70 mg/m2 d 2 plus Pegfilgrastim 6 mg on day 3 every 2 weeks). All were evaluated with CT scan at the baseline, after 4 cycles, at the end of chemotherapy and then every 3 months for two years and 6 months thereafter. Metastatic sites included retroperitoneal nodes, lung, liver and bone. Results: From January 2007, 35 consecutive pts followed in the same oncology institution were included. Male were 74%; median age 65 years; median PS ECOG was 1; Bajorin risk factors was 0 in 37%, 1 in 43%, 2 in 20%. All pts were hospitalized for three days and received chemotherapy with hydration and supportive therapy. After the first 4 cycles of CGP we observed 14.3% CR, 48.6% PR, 22.9% SD and 14.3% PD. After the 4 sequential cycles of M-VAC we observed a global 37.1% of CR, 25.7% of PR, 8.6% of SD and 28.6% of PD. Median TTP was 9.9 months ( 95 % CI, 7.53-14.83) and median OS was 24.27 months ( 95 % CI, 10.03-38.43). Main grade 3–4 toxicity included asthenia ( 27%), anemia (21%), neutropenia (12 %), febrile (9%), thrombocytopenia (9%) and peripheral neuropathy (6 %). After a median follow up of 33 months, 6 of 13 patients who obtained a complete response are free of disease. Conclusions: These data confirm that the sequential use of this two dose-dense regimens is very active and 17 % of patients maintained a CR status.

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