Paclitaxel and carboplatin in patients with metastatic transitional cell cancer of the urinary tract

OBJECTIVES: The combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) is currently considered the most effective chemotherapy for metastatic transitional cell cancer (TCC) of the urinary tract, but because of its considerable toxicity, alternative regimens appear very interesting. We evaluated the efficacy and toxicity of a combination of paclitaxel and carboplatin as first-line therapy for metastatic TCC. METHODS: Thirty-two patients (8 women, 24 men; mean age 67.03 years, range 50 to 79) with metastatic TCC of the bladder or upper urinary tract were included in the study. Paclitaxel (175 mg/m2) was given as a 3-hour intravenous infusion, carboplatin was dosed to an area under the plasma concentration curve of 5 mg/m/min calculated according to the Calvert formula [(creatinine clearance + 25) x 5] as a 30-minute intravenous infusion immediately after paclitaxel. Response evaluation was performed after every 2 cycles and additional therapy depended on response. The maximum number of cycles was 6. RESULTS: With a mean follow-up of 13.1 months (range 2 to 28), 23 of 32 patients responded to treatment (response rate 71.9%), with 31.3% complete remission (CR) (10 of 32) and 40.6% partial remission (PR) (13 of 32). Four patients (12.5%) had stable disease, and 5 patients (15.6%) showed progression. These results compare well with the outcome after MVAC. Toxicity was mainly characterized by neurotoxicity grade 3 and 4 in 9.4%, grade 3 and 4 leukopenia in 37.5%, and grade 3 thrombocytopenia in 3.1% of the patients. No nephrotoxicity was observed, but all patients developed alopecia. Time to progression after CR was a mean of 7.0 months (range 4 to 13) and after PR a mean of 5.9 months (range 2 to 9). CONCLUSIONS: Paclitaxel/carboplatin is an effective therapy for metastatic TCC, with low toxicity.     

An unusual case of transitional cell carcinoma of renal pelvis presenting with brain metastases

We report a rare case, who had presented with a constellation of neurological symptoms (due to multiple brain metastases), but without any urological symptoms, to the department of neurosurgery. The patient was managed with gamma knife stereotactic radiosurgery for the metastatic lesions. During an evaluation for primary, he was found to be having transitional cell carcinoma (TCC) of right renal pelvis, for which palliative radical nephroureterectomy was performed, following which he received four cycles of paclitaxel and carboplatin chemotherapy. The patient is alive with stable disease at 22-months follow-up.     

Phase II study of carboplatin in locally advanced and metastatic transitional cell carcinoma of the urinary bladder

Twenty-five previously untreated patients with measurable locally advanced and/or metastatic transitional cell carcinoma of the urinary bladder were included in a phase II study with carboplatin. Bolus injections were administered in 2 courses every 4 weeks at an initial dose of 400 to 450 mg/m2 with the option of increasing the dose to 450 to 500 mg/m2 in individual patients during the second cycle, depending on haematological toxicity. Two patients had a complete response (CR), 13 showed no change (NC) and 9 had progression of disease (PD), including 4 early progressions. There was no delay in treatment because of myelosuppression. Thrombocytopenia led to a reduction in drug dosage. No reduction in renal function was observed. Increased dosage did not increase the response rate. This study indicated the low effectiveness of single agent carboplatin in transitional cell carcinoma of the urinary bladder.     

Weekly paclitaxel and carboplatin against advanced transitional cell cancer after failure of a platinum-based regimen

OBJECTIVE: Weekly administration of paclitaxel plus carboplatin is hypothesized to be an effective second-line treatment for advanced transitional cell cancer after failure of platinum-based regimen. In this phase 2 trial, we tested this hypothesis. PATIENTS AND METHODS: Patients with advanced transitional cell cancer who showed evidence of progressive or recurrent disease after methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) therapy were eligible for this study. Weekly paclitaxel (80mg/m(2)) and carboplatin (AUC 2) were administered on days 1, 8, 15, 22, 29, and 36; the cycle was repeated every 7 wk until disease progression or intolerable toxicity (maximum 18 doses). RESULTS: Thirty-five patients entered this study. Among the 31 patients who were assessable, 10 had an objective response (overall response rate: 32.3%, 95% confidence interval, 15.8-48.7%). The median progression-free survival (PFS) and median survival times were 3.7 and 7.9 mo, respectively. Among the 22 patients who received prior MVAC therapy for metastatic disease, 36% had an objective response; their median PFS and median survival times were 4.3 and 7.9 mo, respectively; neither survival time significantly differed from the survival time of those who received prior MVAC as adjuvant setting. Toxicities were mild except one toxic death due to neutropenic sepsis. CONCLUSIONS: Weekly paclitaxel plus carboplatin was a manageable, active second-line treatment for advanced transitional cell cancer after failure of platinum-based therapy.     

Long-Term Partial Remission with Capecitabine/Trastuzumab in a Patient with Metastatic Breast Cancer Following Progression on Trastuzumab Alone

BACKGROUND: Since the introduction of trastuzumab into the treatment of Her-2/neu-positive metastatic breast cancer, cases of long-term survival have become more frequent. Even after tumor progression, trastuzumab seems to retain its antitumor activity which is potentiated by the combination with a chemotherapeutic agent. CASE REPORT: We are reporting about the unusual clinical course of a young patient with Her-2/neu-positive breast cancer, who experienced progression of pulmonary and bone metastases under treatment with trastuzumab. Upon progression, a combination therapy with capecitabine/trastuzumab was initiated, and a partial remission was achieved which has continued for over 4 years. CONCLUSION: This unusual clinical course shows that continuing trastuzumab-based therapy beyond progression is a safe, effective, and well-tolerated option which can induce long-term remissions in some patients with Her-2/neu-positive metastatic breast cancer.     

Cis-platin and methotrexate in the treatment of transitional cell carcinoma of the urinary tract

Nineteen patients with recurrent or metastatic transitional cell carcinoma of the urinary tract were treated with a 3-weekly combination of methotrexate 200 mg/m2 as a 24-h infusion with folinic acid rescue and cis-platin 100 mg/m2. An objective response rate of 68% was obtained, with 4 patients (21%) achieving complete remission. Pulmonary disease and lymph node metastases were particularly sensitive to this therapy. The median duration of response was 21 weeks with a median survival of 54 weeks in the responding patients. This regimen warrants further investigation in the treatment of invasive bladder carcinoma.     

Successful treatment of pulmonary metastatic salivary ductal carcinoma with trastuzumab-based therapy

BACKGROUND: Salivary ductal carcinoma (SDC) is an uncommon malignant tumor of the salivary glands. Although there is no known standard of care for the treatment of advanced disease, the vast majority of patients with SDC may be offered palliative systemic therapy. We report a case of epidermal growth factor receptor 2 (HER2)-positive metastatic submandibular SDC with a complete and durable clinical response to treatment with trastuzumab in combination with chemotherapy. METHODS AND RESULTS: A 62-year-old man was diagnosed with SDC of the left submandibular gland with extensive cervical lymph node involvement. The lesion was completely resected, and the patient underwent postoperative radiotherapy. After 6 months, multiple pulmonary metastatic lesions were detected. A complete response was reached with trastuzumab-based combination therapy, and no evidence of disease progression has been observed after 14 months of initiation of systemic therapy. CONCLUSION: Trastuzumab-based combination therapies should be considered for advanced SDC.     

Randomized phase II evaluation of carboplatin and CHIP in advanced transitional cell carcinoma of the urothelium. The Eastern Cooperative Oncology Group

A total of 83 patients with metastatic transitional cell carcinoma who had previously received no systemic therapy entered a randomized phase II evaluation of carboplatin and cis-dichloro-transdihydroxy-bis-isopropylamine platinum IV (CHIP), administered respectively at 400 and 270 mg./m.2 every 28 days. Among evaluable patients with measurable disease response rates were 3 of 22 (14%, 95% confidence interval 5 to 35%) for carboplatin and 4 of 25 (16%, 95% confidence interval 5 to 36%) for CHIP. Among 17 patients with evaluable but not measurable metastases (10 carboplatin and 7 CHIP recipients) there were no responses. Median survival for 64 evaluable patients was 4.8 months (5.0 months for carboplatin and 4.3 months for CHIP recipients). Independent factors prognostic for survival (p less than 0.01) were performance status (0 or 1 versus 2 or 3), liver metastases, prior radiation therapy and recent weight loss (p = 0.02). Multivariate analysis confirmed that a performance status of 2 or 3 and liver metastases were predictive of shorter survival. A total of 31% of the patients treated with carboplatin and 34% of those who received CHIP experienced severe or life-threatening myelosuppression. While the response rates with carboplatin and CHIP are modest, we believe that the characteristics of these agents indicate that they should be evaluated further.     

Response of bilateral choroidal metastases of breast cancer to therapy with trastuzumab

Intraocular metastases, especially those of the choroidal plexus, are not common in metastatic breast cancer patients and are typically associated with a poor prognosis and impaired quality of life. A 45-year-old woman with breast cancer overexpressing HER2 and metastasizing to choroidal plexus, lymph nodes and skin received a combination of trastuzumab and paclitaxel as first-line treatment. Subsequently, at progression, trastuzumab was reintroduced together with vinorelbine. Administration of trastuzumab with either paclitaxel or vinorelbine led to a rapid improvement of the ocular symptoms, associated with a rapid objective response of all metastatic lesions and a prompt improvement in the quality of life. Choroidal metastases from breast cancer overexpressing HER2 are responsive to trastuzumab and chemotherapy (paclitaxel or vinorelbine). The susceptibility of ocular metastases to this approach seems different to that of other sanctuary disease sites.     

Phase II trial of weekly paclitaxel and carboplatin chemotherapy in patients with advanced transitional cell cancer

OBJECTIVE: We investigated the efficacy and toxicity of a first-line combination chemotherapy using weekly paclitaxel and carboplatin in patients with metastatic transitional cell cancer (TCC). PATIENTS AND METHODS: Thirty-three patients with advanced measurable TCC of the urothelium were entered onto this trial. Patients were treated once weekly with a combination therapy of paclitaxel (100mg/m(2)) and carboplatin (AUC 2, according to the Calvert formula). Therapy courses were administered for six consecutive weeks. After two cycles, a re-staging was carried out to evaluate response. RESULTS: Objective response rate was 57.6% with 6 complete (18.2%) and 13 partial remissions (39.4%). Seven patients had stable disease (21.2%) and 7 patients had progressed at the first evaluation of response (21.2%). Median progression-free interval and median survival was 6.5 (1-35) and 12 (2.5-58) months, respectively. Toxicity was moderate and manageable with grade 3 and 4 neutropenia in 8 patients (24%), but no case of neutropenic fever. Other hematological grade 3 toxicities occurred in 9 patients (27%) and grade 3 peripheral neuropathy in 2 patients (6%). There was no treatment-related death. Dose reduction or short delay of treatment was necessary in 3 patients. CONCLUSIONS: Combination therapy using weekly paclitaxel and carboplatin was active in patients with advanced TCC and adverse prognostic features. The weekly dosing used in this trial warrants further investigation as an alternative first-line approach in patients with poor renal reserve and/or performance status or as a second-line management of advanced TCC.     

Serum concentration of laminin in transitional cell carcinoma

The concentration of laminin in the serum was determined for 45 patients with urinary tract transitional cell carcinoma, and the clinical significance of the findings was considered. The difference between the serum laminin concentrations in the control group and the transitional cell carcinoma patient group was not statistically significant, but the serum laminin level was highest in the transitional cell carcinoma patients with metastatic foci. In many of the patients who had metastatic foci and showed clearly progressive disease, the serum laminin concentration was found to increase with the passage of time. When the transitional cell carcinoma tissues were stained by the fluorescent antibody technique, there was little distribution of laminin in the tumor tissues, contrary to our earlier-reported findings regarding the staining of laminin in renal cell carcinoma tissues. In renal cell carcinoma patients, the serum concentration of laminin had been found to be high even when there were no metastatic foci, and consideration of this fact strongly suggests the possibility that the mechanism for laminin synthesis in urinary tract transitional cell carcinoma is different from that in renal cell carcinoma. It was surmised that the serum laminin concentration has potential for use as a diagnostic indicator of metastasis in patients with urinary tract transitional cell carcinoma.     

Retrograde endoscopic laser therapy and ureteroscopic surveillance for transitional cell carcinoma of the upper urinary tract

OBJECTIVE: To investigate the efficacy of endoscopic laser therapy and ureteroscopic surveillance for transitional cell carcinoma (TCC) of the upper urinary tract. Methods: Tumors of the upper urinary tract were detected at ureteroscopy. After TCC was diagnosed by biopsy, retrograde endoscopic laser therapy was performed. Recurrent tumors were treated endoscopically and the patients were followed by ureteroscopic surveillance at 3- to 6-month intervals. RESULTS: Seven patients underwent ureteroscopic treatment. The tumor was grade 1 in five patients and grade 2 in two patients. The average tumor size was 1.3 cm. One patient with large, multifocal tumors died of metastatic disease, and one died of an unrelated cause. One patient requested nephroureterectomy after endoscopic treatment. The remaining four patients were followed up for a mean of 32 months after initial treatment. Each patient received an average of 5.3 ureteroscopic surveillance procedures while 3.3 recurrences on average were detected. Recurrence occurred in all the patients who showed normal radiographic findings. Urine cytology was also of little value in predicting tumor recurrence, except in one patient with carcinoma in situ. The recurrent tumors detected by ureteroscopy were successfully treated by repeated endoscopic procedures. After the follow up, three patients remained alive with no signs indicative of disease, but one patient with an initial grade 2 tumor died of recurrence after 30 months. CONCLUSIONS: Given that ureteroscopic evaluation is essential for surveillance after endoscopic treatment of upper urinary tract TCC because of residual concern about recurrence, patients treated endoscopically should be recommended to undergo long-term endoscopic follow up.     

Response to paclitaxel and carboplatin in metastatic salivary gland cancer: a case report

BACKGROUND: Malignant tumors of the salivary gland are rare entities that are treated primarily by surgical resection. For patients with recurrent or unresectable disease, options include radiation therapy or chemotherapy; however, responses are few and of short duration. Patients with metastatic disease have been treated with chemotherapy, but, again, response rates have been low and of short duration. METHODS: A 52-year-old man was seen with a mass on his tongue. A biopsy revealed adenocarcinoma of a minor salivary gland. Ten months after surgical resection, neck dissection, and radiation therapy, the patient was found to have metastatic disease to the lung. Chemotherapy was initiated with carboplatin and paclitaxel. RESULTS: The patient obtained a complete response after six cycles of carboplatin and paclitaxel. CONCLUSIONS: The use of carboplatin and paclitaxel in the setting of metastatic salivary gland cancer is a viable option.     

Metastatic basal cell carcinoma: rapid symptomatic response to cisplatin and paclitaxel

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in the community, although it rarely metastasizes. The literature reports less than 100 patients who have received chemotherapy for metastatic BCC. A further case of this rare disease is reported here. The pattern of disease in the reported patient was similar to that described in the literature, but the patient experienced a long period with untreated metastatic disease compared with that in the literature. METHOD: The patient was treated with cisplatin in combination with paclitaxel. Literature review suggests this to be the first report of this combination. RESULTS: Rapid symptomatic response was achieved though late neurotoxicity occurred. CONCLUSION: This regimen is an active combination for the rare patient with metastatic BCC. The combination of carboplatin and paclitaxel causes less neurotoxicity and may therefore be a superior regimen.     

Three cases of small cell carcinoma of the urinary bladder: a case report

We report three cases of small cell carcinoma of the urinary bladder. Case 1: A 69-year-old man showed microscopic hematuria during follow up of prostate cancer of stage D2. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage of pT2N0M0. Complete remission was achieved by three courses of chemotherapy consisting of irinotecan and carboplatin. The patient was died by prostate cancer 16 months after the chemotherapy. Case 2: An 83-year-old woman presented with macroscopic hematuria. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage of pT2N0M0 and partial cystectomy was performed. The patient has been alive without any evidence of tumor recurrence at 6 months after surgery. Case 3: An 84-year-old man presented with macroscopic hematuria. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage ofcT3bN0M1 with multiple liver metastases. Complete remission was achieved by three courses of chemotherapy consisting of etoposide and carboplatin.     

Clear cell adenocarcinoma arising from abdominal wall endometriosis mimicking urachal tumor

A 41-year-old woman presented with severe lower abdominal pain. She had a history of 2 cesarean deliveries. Magnetic resonance imaging (MRI) revealed a 4.3 × 4.6 × 4.8-cm mass on the urinary bladder dome. Preoperative diagnosis was invasive urachal tumor. Wide resection of the tumor was performed. The histopathological diagnosis was clear cell adenocarcinoma with endometriosis. MRI revealed normal-sized ovaries and uterus. The definite diagnosis of clear cell carcinoma arising from abdominal wall endometriosis was made. Adjuvant chemotherapy with paclitaxel and carboplatin (total 6 courses) was planned. The patient has thus far received 4 courses of this treatment.     

Gemcitabine plus cisplatin for advanced transitional cell carcinoma of the urinary tract: a phase II multicenter trial

PURPOSE: We determined the activity and toxicity of gemcitabine plus cisplatin in patients with inoperable or metastatic transitional cell carcinoma of the urinary tract. MATERIALS AND METHODS: A total of 54 patients with transitional cell carcinoma, measurable disease and Eastern Cooperative Oncology Group performance status 2 or greater were enrolled in this multicenter phase II trial. Previous adjuvant or neoadjuvant therapy for locally advanced disease was acceptable if it had been completed more than 1 year before study entry. Every 4 weeks patients received 1,000 mg./m.2 gemcitabine intravenously on days 1, 8 and 15, and 70 mg./m.2 cisplatin intravenously on day 2. RESULTS: All patients were evaluable for response and toxicity. Notably only 7 of the 54 patients (13%) previously received chemotherapy in an adjuvant or neoadjuvant setting. Overall we observed 26 objective responses (48%), of which 15% were complete. Median time to progression was 23 weeks and median survival was 54 weeks. Treatment was well tolerated. The main toxicities were leukopenia (grade 3 in 28% and grade 4 in 11% of patients), anemia (grade 3 in 34% and grade 4 in 6%) and thrombocytopenia (grade 3 in 14% and grade 4 in 6%). Other relevant side effects were nausea and vomiting in 20% of cases, fever in 24%, alopecia in 22%, renal failure in 7.4% and mucositis in 2%. CONCLUSIONS: Combined cisplatin plus gemcitabine is highly active in advanced transitional cell carcinoma of the urinary tract with manageable toxicity. The response rate, time to treatment failure and overall survival appeared to be comparable to those achieved with combined methotrexate, vinblastine, doxorubicin and cisplatin. Conversely toxicity appeared lower. Evaluation of this regimen in randomized studies with methotrexate, vinblastine, doxorubicin and cisplatin is strongly suggested.     

Carboplatin plus paclitaxel therapy after docetaxel in men with metastatic castrate resistant prostate cancer

Objectives

Docetaxel is considered first-line chemotherapy for patients with metastatic castrate resistant prostate cancer (CRPC). Carboplatin and paclitaxel have demonstrated activity in CRPC but published data are limited regarding use after docetaxel.

Methods

A retrospective, bi-institutional review was conducted of patients with advanced CRPC treated with carboplatin plus paclitaxel after docetaxel. Therapy was evaluated for tolerability, response, and survival. Endpoints used modified Prostate Cancer Working Group 2 criteria.

Results

Twenty-five patients were identified from February 2000 to March 2008. Median pretreatment PSA was 130.2 ng/ml [range 0.1–2100]. Sites of metastases included bone (88%), lymph nodes (52%), pelvis (32%), lung (28%), and liver (20%). A median 4.5 cycles of docetaxel [range 1–22] were given with a median progression-free survival (PFS) of 12 weeks [range 2–68]. Eighty-eight percent of patients (22/25) were docetaxel-refractory at the initiation of therapy with carboplatin (AUC 4–6) day 1 plus paclitaxel 60–80 mg/m² days 1, 8, and 21 recycled every 28 days. Patients received a median of 3.5 cycles [range 1–8] of carboplatin/paclitaxel with a median PFS of 12 weeks [range 2–35]. Sixty-four percent of patients (16/25) achieved ≥30% reduction in PSA with a median overall survival of 42 weeks [95% CI 30.6–53.5 weeks]. Grade 3 or 4 adverse hematologic events occurred in 11/25 (44%) patients, with no neutropenic fever or grade 3/4 non-hematologic toxicity.

Conclusion

Carboplatin/paclitaxel chemotherapy following docetaxel in metastatic CRPC is well tolerated with favorable PSA response rates and survival. This combination is a viable option after progression on docetaxel-based therapy.     

Contribution of 11C-choline positron emission tomography/computerized tomography to preoperative staging of advanced transitional cell carcinoma

PURPOSE: Current imaging modalities for preoperative staging of advanced transitional cell carcinoma of the bladder or upper urinary tract are not sensitive for detection of metastases. This study examines the contribution of 11C-choline positron emission tomography/computerized tomography to preoperative staging of transitional cell carcinoma. MATERIALS AND METHODS: We prospectively evaluated 18 patients with 19 advanced transitional cell carcinomas (17 bladder tumors and 2 upper tract transitional cell carcinomas). All patients had computerized tomography of the chest, abdomen and pelvis negative for metastases. 11C-choline positron emission tomography/computerized tomography was performed on a Discovery ST(R) positron emission tomography/computerized tomography system. Finally 16 patients underwent radical surgery and positron emission tomography/computerized tomography images were compared to histopathological findings. Two patients were not operated on due to the findings on 11C-choline positron emission tomography/computerized tomography. RESULTS: 11C-choline uptake was found in all primary transitional cell carcinomas, with a maximum standardized uptake value of 7.3 +/- 3.2 (mean +/- SD). The series included 3 patients with refractory bladder carcinoma in situ, which was visualized in all 3, with a standardized uptake value of 6.9 +/- 5.6. In 6 patients uptake of 11C-choline in lymph nodes as small as 5 mm was visualized (standardized uptake value 3.8 +/- 1.4). Of these patients 4 underwent surgery and histopathology confirmed malignancy in 3 of 4. No additional patients with positive lymph nodes were found on histopathology. Metastases were visualized in bones with normal architecture on computerized tomography in 4 patients (standardized uptake value 5.2 +/- 1.1) and were confirmed by followup computerized tomography. CONCLUSIONS: In this small series 11C-choline positron emission tomography/computerized tomography was highly sensitive for primary and metastatic transitional cell carcinoma. Carcinoma in situ, lymph node metastases and early bony metastases were visualized. 11C-choline positron emission tomography/computerized tomography is a promising tool for preoperative staging of advanced transitional cell carcinoma.     

Paclitaxel,Carboplatin, and Trastuzumab in a Neo‐adjuvant Regimen for HER2‐positive Breast Cancer

To evaluate a nonanthracycline‐containing regimen consisting of 24 weekly administrations of paclitaxel, carboplatin, and trastuzumab as neo‐adjuvant therapy for human epidermal growth factor receptor 2 (HER2)‐positive breast cancer. Patients with stage II or III breast cancer, including inflammatory disease, with HER2 overexpression (immunohistochemistry and/or fluorescent in situ hybridization) were treated with 24 weekly administrations of paclitaxel 70 mg/m², carboplatin AUC = 3 mg/mL/minute, and trastuzumab 2 mg/kg (loading dose 4 mg/kg). In cycles 7, 8, 15, 16, 23, and 24, only trastuzumab was given. The primary end point was pathologic complete response (pCR) in both breast and axilla. Of 61 evaluable patients, 61% had stage II disease and 75% were node‐positive. The median NRI (Neoadjuvant Response Index, a measure of the degree of downstaging by chemotherapy) of all patients was 0.86. Twenty‐seven (44%) had a NRI of 1.0, which corresponds to pCR in breast and lymph nodes. The most commonly reported grade 3/4 toxicities were neutropenia (72%) and thrombocytopenia (36%). Dose reduction was necessary in 51% of the patients. A weekly carboplatin–paclitaxel–trastuzumab neo‐adjuvant regimen is highly active in HER2‐positive breast cancer with an acceptable toxicity profile. A multicenter phase 2 trial has recently reached its accrual target and will serve as a basis for a subsequent randomized phase 3 study comparing this regimen to a similar regimen preceded by anthracyclines.