Bladder Cancer

This is a timely review on thecurrent status of selective bladderpreservation for muscleinvasivebladder cancer. Although controversial,the concept is extremely attractiveto patients, and evidence fromretrospective and/or small series demonstrateits efficacy. Most of these trials,however, have included highlyselected patients. Unfortunately, thereare few, if any, ongoing randomizedcontrolled trials comparing radical cystectomyto bladder-preserving protocols.Although the overall 5-yearsurvival rate for radical cystectomy andtrimodality therapy is approximately50%, patients with pure T2 disease frequentlyachieve 5-year survival ratesapproaching 70%.[1-3] While it is clearlybeyond the scope of this editorial togo into an in-depth analysis of all thestudies reported to date, several significantquestions remain.

While organ preservation with nonextirpative surgery, radiotherapy,and frequently, chemotherapy has become a favored strategy in thetreatment of many cancers, bladder preservation for patients with invasivedisease remains controversial. The standard treatment for muscleinvasivebladder cancer in the United States is still radical cystectomywith pelvic lymph node dissection. An alternative to cystectomy ismultimodality bladder preservation with thorough transurethral resection,chemotherapy, and radiation therapy. This review will addressissues raised by a multimodality approach for the treatment of invasivebladder cancer.

Currently, the four-drug combination of methotrexate, vinblastine,doxorubicin (Adriamycin), and cisplatin (MVAC) or the two-drug combinationof gemcitabine and cisplatin (GC) represents the standard ofcare for patients with locally advanced and metastatic transitional cellcarcinoma of the urothelium. Recently, there has been a plethora ofdata from other chemotherapeutic regimens. Promising new agents,such as the multitargeted antifolate pemetrexed (Alimta), and new drugcombinations have demonstrated increased efficacy and/or decreasedtoxicity compared with current regimens. Currently, data are availablefrom three phase II studies utilizing pemetrexed or the combination ofpemetrexed/gemcitabine (Gemzar) in patients with locally advanced andmetastatic transitional cell carcinoma of the urothelium. Further investigationof combinations of pemetrexed and other active drugs inthe treatment of patients with locally advanced and metastatic diseaseis warranted.

Pemetrexed (Alimta) is an antifolate that is effective in the inhibitionof multiple enzyme targets including thymidylate synthase,dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase.The compound has been evaluated in several phase I trials, bothas single agent and in combination with other cytotoxic agents. Theinitial schedule selected for further investigation in phase II trials waspemetrexed 600 mg/m2 as a 10-minute infusion on day 1 every 21 days.During the subsequent phase II development, the dose of pemetrexedwas adjusted to 500 mg/m2 due to bone marrow and gastrointestinaltoxicities. The adjusted dose of pemetrexed was well tolerated throughoutthe late-phase drug development program. Preclinical evidencesuggests that pemetrexed has additive or synergistic activity when combinedwith many other clinically important anticancer agents, includinggemcitabine (Gemzar), fluorouracil, carboplatin (Paraplatin),oxaliplatin (Eloxatin), paclitaxel, and vinorelbine (Navelbine). Doselimitingtoxicities in these studies were primarily hematologic, and therewas no evidence of cumulative hematologic toxicity. During the drugdevelopment program it was discovered that supplementation with folicacid and vitamin B12 profoundly increased the tolerability ofpemetrexed. The studies discussed in this review demonstrate thatpemetrexed is well tolerated as a single agent and will be an importantcontribution to combination chemotherapy regimens.

The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.

NEWTON, Massachusetts-Matritech Inc has launched its new point-of-care diagnostic test for bladder cancer-NMP22 BladderChek. Cytogen Corporation (Princeton, New Jersey) will distribute the product.

BETHESDA, Maryland-The National Cancer Institute’s Kidney/Bladder Cancer Progress Review Group has released 13 priority recommendations intended to serve as a national plan to guide research in the two diseases over the next 5 years. The recommendations cover basic and translational research, cancer control, and cancer treatment, and range from understanding the biologic mechanisms underlying the two diseases to developing innovative strategies to eradicate them.

NEWTON, Mass-Matritech Inc. has received clearance from the US Food and Drug Administration to market NMP22 BladderChek for monitoring patients with a history of bladder cancer.

In less than a decade, docetaxel (Taxotere) has progressed from initial studies in anthracycline-refractory metastatic breast cancer to several large, phase III randomized trials evaluating its efficacy as adjuvant, neoadjuvant, and first-line therapy for metastatic breast cancer, non-small-cell lung cancer (NSCLC), and ovarian cancer. In other tumor types, including prostate, head and neck, gastric, and bladder cancer, ongoing phase III trials are comparing docetaxel-containing regimens to previously established regimens. For the seven tumor types reviewed in this supplement, phase III study information for docetaxel or docetaxel-based combinations are presented. Impressive results have been consistently demonstrated in the trials reported to date.

The multistep process of carcinogenesis, which can take many years, provides many opportunities for intervention to inhibit disease progression. Effective chemoprevention agents may reduce the risk of cancer by inhibiting the initiation stage of carcinoma through induction of apoptosis or DNA repair in cells harboring mutations, or they may act to prevent promotion of tumor growth. Similarly, chemoprevention may entail blocking cancer progression to an invasive phenotype.

Among the most exciting new anticancer products presented at the 2001 ASCO meeting were new drugs that block the epidermal growth factor receptor (EGFR). About 30% to 90% of carcinomas express high levels of EGFR. These include, among others, head and neck cancer, lung cancer, pancreatic cancer, colon cancer, breast cancer, ovarian cancer, and bladder cancer.

Fenretinide (N-4-hydroxyphenyl-retinamide, or 4-HPR) is a semisynthetic retinoid that was initially developed as a low-dose chemopreventative agent.[1-3] Unlike other naturally occurring retinoids such as all-trans, 13-cis, and 9-cis retinoic acids, fenretinide does not induce systemic catabolism that interferes with the maintenance of effective plasma levels during long-term use. This characteristic, combined with the agent’s low toxicity and its ability to block aspects of carcinogenesis, provided the rationale for the development of fenretinide in lower doses as a chemoprevention agent for breast, prostate, and bladder cancer.

Conventional histopathologic evaluation of bladder cancer, encompassing tumor grade and stage, is inadequate to accurately predict the behavior of most bladder tumors. Intense research efforts are under way to identify and

ANAHEIM, California-A phase III Intergroup trial has provided strong evidence that neoadjuvant MVAC-methotrexate, vinblastine, doxorubicin (Adriamycin), cisplatin (Platinol)-provides a survival benefit in patients with locally advanced bladder cancer, David Crawford, MD, said at the American Urological Association (AUA) annual meeting (abstract 1069).

Conventional histopathologic evaluation of bladder cancer, encompassing tumor grade and stage, is inadequate to accurately predict the behavior of most bladder tumors. Intense research efforts are under way to identify and

Conventional histopathologic evaluation of bladder cancer, encompassing tumor grade and stage, is inadequate to accurately predict the behavior of most bladder tumors. Intense research efforts are under way to identify and

Conventional histopathologic evaluation of bladder cancer, encompassing tumor grade and stage, is inadequate to accurately predict the behavior of most bladder tumors. Intense research efforts are under way to identify and

ANAHEIM, California-In patients with superficial bladder cancer, it is possible to optimize treatment with mitomycin (Mutamycin) by enhancing the drug concentration in urine, according to the results of a multicenter study presented at the American Urological Association annual meeting (abstract 776).

In a recent issue of ONCOLOGY (15:85-88, 2001), Drs. Edgar C. Baselli and Richard E. Greenberg presented a brief

Drs. Vaughn and Malkowicz have provided us with a succinct, thorough, evidence-based overview of the current role of chemotherapy in advanced bladder cancer. Their discussion highlights the veritable explosion of new chemotherapy agents

Drs. Vaughn and Malkowicz provide a fairly extensive and balanced review of chemotherapy for metastatic bladder cancer. They highlight the results obtained with some of the most commonly employed regimens that have been evaluated

Invasive bladder cancer is a chemotherapy-sensitive neoplasm. Historically, the development of cisplatin (Platinol)-based chemotherapy regimens has represented an important advance for patients with metastatic

BOSTON-A combination of transurethral resection (TUR) and radiochemotherapy with cisplatin (Platinol) and fluorouracil (5-FU) produced the most promising results in a German study of bladder-sparing protocols for patients with invasive bladder cancer.

CARPINTERIA, Calif-A newly available fluorescent-based immunocytologic test to detect superficial bladder cancer, ImmunoCyt, used in conjunction with urinary cytology, will likely reduce the need for periodic cystoscopies in patients with transitional cell bladder cancer and enhance the early detection of recurrent disease.

Transurethral resection remains the standard for first-line treatment of transitional cell carcinoma of the bladder. This technique clearly defines the pathologic grade and is essential in determining the clinical stage of