Cisplatin, Cyclophosphamide and Doxorubicin Chemotherapy for Unresectable Urothelial Tumors: The M. D. Anderson Experience

Abstract

We reviewed retrospectively 97 patients treated with cisplatin, cyclophosphamide and doxorubicin chemotherapy at our hospital to evaluate predictive variables for response to chemotherapy and long-term survival free of disease. Histological subtype influenced response: 70 per cent of the patients with pure transitional cell carcinoma achieved an objective response (partial remission 31 per cent and complete remission 39 per cent), whereas 45 per cent of those with mixed tumors achieved response (partial remission 20 per cent and complete remission 25 per cent). Patients with nodal metastases only had an equal over-all response rate to those with visceral metastasis (64 versus 62 per cent) but patients with nodal metastases had a higher complete remission rate (45 versus 20 per cent). A total of 35 patients (36 per cent) achieved a complete response. In 17 of the 35 patients the duration of response was less than 100 weeks and 18 (51 per cent) have survived longer than 100 weeks. Of the 17 patients with a survival free of disease of less than 100 weeks 16 died of recurrent urothelial tumors and 1 died of a second primary tumor. Among the patients with a survival free of disease of longer than 100 weeks only 2 have had recurrent urothelial tumors; 72 per cent of the patients in this category remain free of disease. Patients with pure transitional cell carcinoma were represented in equal frequency among patients achieving a durable complete remission and those with a complete remission of less than 100 weeks. These data demonstrate the ability of cisplatin, cyclophosphamide and doxorubicin combination chemotherapy to achieve a complete remission and long-term survival free of disease among select patients with unresectable urothelial tumors.

Squamous Cell Carcinoma of the Urinary Bladder

“…7 The development of more effective modalities to reduce deaths from localized disease, such as preoperative radiotherapy and adjuvant chemotherapy, may improve the results in transitional cell carcinoma but not in squamous tumors. 6,[38][39][40][41] When considering the progress with orthotopic bladder replacement, like the urethral Kock pouch adopted in five patients in this work, the acceptance of patients for surgical treatment had improved. The current treatment modalities do not alter the dismal prognosis of those unfortunate patients diagnosed with far-advanced disease.…”

Does Squamous Differentiation Portend Worse Outcomes in Urothelial Bladder Cancer?

“…While recent studies have found certain variants such as micropapillary and plasmacytoid to act more aggressively, SQD has been historically described to act similarly to NV histology 5,11,14,15,18,19 . However, much of the SQD literature draws on older cohorts.…”

“…Although SQD was previously shown to be associated with higher pathologic staging and increased risk of local recurrence, when accounting for stage, SQD does not alter overall survival (OS) or disease-specific survival (DSS) 7,8,[11][12][13] . Furthermore, there is evidence suggesting that SQD may be equally sensitive to chemotherapy as non-variant (NV) urothelial bladder cancer 10,12,[14][15][16][17] .…”

Activation of Murine Peritoneal Macrophages with Cisplatin and Lipopolysaccharide: Involvement of Protein Kinase C and Tyrosine Kinase.

“…Cisplatin [cis-dichlorodiamine platinum (II)], a potent antitumor compound, has been used successfully against a number of tumors in animals and human cancers [10][11][12]. This compound has been reported to activate murine peritoneal and bone marrow-derived macrophages to the tumoricidal state [13][14][15], in which state the cells show increased production of interleukin-1 (IL-1) and tumor necrosis factor (TN F) [16], reactive oxygen metabolites [17,18], reactive nitrogen intermediates [19], lysozyme, and arginase [20].…”