Biomedical Engineering Reference
In-Depth Information
Intravesical therapies, such as bacillus Calmette-Guérin (BCG)
immunotherapy and mitomycin C (MMC) chemotherapy, can
prevent these local recurrences and are therefore recommended
as adjuvant therapy for high-risk patients after transurethral
resection of the bladder tumor (TURBT) (Herr et al. 1988, Herr
et al. 1995, Malmstrom et al. 2009, Shelley et al. 2003, Shelley et
al. 2000, Sylvester et al. 2005). Unfortunately, despite receiving
intravesical therapy many patients (>50%) will experience a local
recurrence of cancer. More importantly, 15-30% will progress to
muscle-invasive bladder cancer (MIBC), a disease that carries a
five-year mortality rate of ~50% (Addeo et al. 2010). Improving
bladder cancer patient survival and quality of life requires three
things: (1) a truly effective treatment that can prevent local
recurrences of NMIBC, (2) thwart the progression of NIMBC
to MIBC, and (3) a therapy that can eradicate MIBC once it has
arisen and thereby prevent its spread to distant organ sites. Our
current development includes a mitomycin C containing LTSL,
which we intend to take forward for treatment of nonmuscle
invasive bladder cancer. The rationale for this will be to use ther-
mal enhancement of cell killing that is achieved with mitomycin
C, combined with an approach that we believe will enhance pen-
etration depth of the drug into the bladder wall, thereby reduc-
ing likelihood for local recurrence. A randomized phase III
trial has been previously reported indicating that intravesicular
mitomycin C with local hyperthermia can prolong progression
free survival in patients with nonmuscle invasive bladder cancer
(Colombo et al. 2011). We believe that this success can be further
built upon by using a liposomal formulation of mitomycin C.
The neoadjuvant combination of cisplatin and gemicitabine,
followed by cystectomy, is the current standard of care for treat-
ment of muscle invasive bladder cancer. For MIBC, current
neoadjuvant chemotherapy regimens only increase five-year
survival by about 5% over surgery alone (Shariat et al. 2006).
Thus, there is a need to improve survival. There is evidence that
increasing the pathologic complete response (CR) rate has a
positive influence on progression free survival (Sawhney et al.
2006). The rationale for using the LTSL-cisplatin in this setting
will be to increase the pathologic CR rate.
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Colombo, R., Salonia, A., Leib, Z., Pavone-Macaluso, M.,
Engelstein, D. 2011 Long-term outcomes of a random-
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references
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