GASTROINTESTINAL CANCERS
Colorectal
cancer (CRC) is the most common type of gastrointestinal malignancy. Nearly
145,000 new cases are diagnosed each year in the USA; worldwide, nearly one
million cases are diagnosed each year. At the time of initial presentation,
only about 40–45% of patients are potentially curable with surgery. Patients
presenting with high-risk stage II disease and stage III disease are candidates
for adjuvant chemotherapy with an oxaliplatin-based regimen in com-bination with
5-FU plus leucovorin (FOLFOX or FLOX) or with oral capecitabine (XELOX) and are
generally treated for 6 months following surgical resection. Treatment with
this combination regi-men reduces the recurrence rate after surgery by 35% and
clearly improves overall patient survival compared with surgery alone.
Significant advances
have been made over the past 10 years with respect to treatment of metastatic
CRC. There are four active cytotoxic agents—5-FU, the oral fluoropyrimidine
capecitabine, oxaliplatin, and irinotecan; and three active biologic agents—the
anti-VEGF antibody bevacizumab and the anti-EGFR antibodies cetuximab and
panitumumab. In general, a fluoropyrimidine with either intravenous 5-FU or
oral capecitabine serves as the main foundation of cytotoxic chemotherapy
regimens. Recent clinical studies have shown that FOLFOX/FOLFIRI regimens in
combi-nation with the anti-VEGF antibody bevacizumab or with the anti-EGFR
antibody cetuximab result in significantly improved clinical efficacy with no
worsening of the toxicities normally observed with chemotherapy. In order for
patients to derive maxi-mal benefit, they should be treated with each of these
active agents in a continuum of care approach. Using this strategy, median
survivals now are in the 24–28 month range, and in some cases, approach 3
years. One of the main challenges facing clinicians at present is to begin to
identify which patients would benefit from these various cytotoxic and biologic
agents as well as identify those who might experience increased toxicity.
The incidence of
gastric cancer, esophageal cancer, and pancre-atic cancer is much lower than
for CRC, but these malignancies tend to be more aggressive and result in
greater tumor-related symptoms. In most cases, they cannot be completely
resected surgically, as most patients present with either locally advanced or
metastatic disease at the time of their initial diagnosis. 5-FU-based
chemotherapy, using either intravenous 5-FU or oral capecitabine, is generally
considered the main backbone for regimens targeting gastroesophageal cancers.
In addition, cisplatin-based regimens in combination with either irinotecan or
one of the taxanes (pacli-taxel or docetaxel) also exhibit clinical activity.
Response rates in the 40–50% range are now being reported. Recent studies have
shown that the addition of the biologic agent trastuzumab to
cis-platin-containing chemotherapy regimens provides significant clinical
benefit in gastric cancer patients whose tumors overexpress the HER-2/ neu receptor. In addition, neoadjuvant
approaches with combination chemotherapy and radiation therapy prior to surgery
appear to have promise in selected patients.
Although
gemcitabine is approved for use as a single agent in metastatic pancreatic
cancer, the overall response rate is less than 10%, with complete responses
being quite rare. Intense efforts con-tinue to be placed on incorporating
gemcitabine into various com-bination regimens and on identifying novel agents
that target signal transduction pathways thought to be critical for the growth
of pan-creatic cancer. One such agent is the small molecule inhibitor
erlo-tinib, which targets the EGFR-associated tyrosine kinase. This agent is
now approved for use in combination with gemcitabine in locally advanced or metastatic
pancreatic cancer although the improvement in clinical benefit is relatively
small. There is also evidence to sup-port the use of adjuvant chemotherapy with
either single-agent gemcitabine or 5-FU/leucovorin in patients with early-stage
pancre-atic cancer who have undergone successful surgical resection.
Related Topics
Privacy Policy, Terms and Conditions, DMCA Policy and Compliant
Copyright © 2018-2024 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.