Table Of ContentNEOADJUVANT
CHEMOTHERAPY –
CURRENT APPLICATIONS
IN CLINICAL PRACTICE
Edited by Oliver F. Bathe
Neoadjuvant Chemotherapy – Current Applications in Clinical Practice
Edited by Oliver F. Bathe
Published by InTech
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First published January, 2012
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Neoadjuvant Chemotherapy – Current Applications in Clinical Practice,
Edited by Oliver F. Bathe
p. cm.
ISBN 978-953-307-994-3
Contents
Preface IX
Chapter 1 Neoadjuvant Systemic Therapy in Breast Cancer 1
Vladimir F. Semiglazov and Vladislav V. Semiglazov
Chapter 2 Neoadjuvant Therapy in Breast Cancer 23
Angela Lewis Traylor, Nathalie Johnson and Esther Han
Chapter 3 Surgical Intervention Following Neoadjuvant
Chemotherapy in Breast Cancer 31
Michelle Sowden, Baiba Grube, Brigid Killilea and Donald Lannin
Chapter 4 Neoadjuvant Chemotherapy in Extra-Pulmonary
Neuroendocrine Carcinoma 41
Halfdan Sorbye
Chapter 5 Neoadjuvant Chemotherapy in Gynecologic Cancers 59
Prapaporn Suprasert
Chapter 6 Neoadjuvant Chemotherapy in Ovarian Cancer 73
Jasmeet Chadha Singh and Amy Tiersten
Chapter 7 Neoadjuvant Chemotherapy
in the Treatment of Cervical Cancer 81
Lua Eiriksson, Gennady Miroshnichenko and Allan Covens
Chapter 8 Percutaneous Pelvic Perfusion with
Extracorporeal Chemofiltration for
Advanced Uterine Cervical Carcinoma 109
Takeshi Maruo, Satoru Motoyama, Shinya Hamana,
Shigeki Yoshida, Masashi Deguchi,
Mineo Yamasaki and Yanson Ku
Chapter 9 Neoadjuvant Treatment for Oesophago-Gastric Cancer 123
John E. Anderson and Jo-Etienne Abela
VI Contents
Chapter 10 Developments in Neoadjuvant Chemotherapy
and Radiotherapy in Rectal Cancer 135
Sofia Conde, Margarida Borrego and Anabela Sá
Chapter 11 Neoadjuvant Chemotherapy
for Colorectal Liver Metastases 157
Pamela C. Hebbard, Yarrow J. McConnell and Oliver F. Bathe
Chapter 12 Chemotherapy in the Combined Modality
Treatment of Penile Carcinoma 181
Jennifer Wang and Lance C. Pagliaro
Chapter 13 Neoadjuvant Chemotherapy for Soft Tissue Sarcoma
of the Extremity or Trunk, Gastrointestinal Stromal
Tumors, and Retroperitoneal Sarcoma 193
Lloyd Mack and Walley Temple
Chapter 14 Effects of Neoadjuvant Chemotherapy in High-Grade
Non-Metastatic Osteosarcoma of Extremities 213
Milan Samardziski, Vesna Janevska, Beti Zafirova-Ivanovska,
Violeta Vasilevska and Slavica Kraleva
Chapter 15 Chemotherapy and Mechanisms
of Resistance in Breast Cancer 235
Andre Lima de Oliveira, Roberto Euzebio dos Santos
and Fabio Francisco Oliveira Rodrigues
Preface
It was not so long ago that the therapeutic mainstays for solid tumors consisted of
surgery and radiation. The discovery that nitrogen mustard and antifolates
(methotrexate) could be used to induce remissions in childhood leukemia (Farber &
Diamond, 1948; Goodman, Wintrobe et al., 1946) heralded a new therapeutic
approach. Since then, the most significant therapeutic advances in oncology have been
related to the discovery of novel systemic agents. In the context of solid tumors,
systemic chemotherapy has allowed the oncologist to address the systemic nature of
cancer, which has frequently metastasized by the time it has manifested clinically.
But with progress, new questions arise. As more agents become available, the most
efficacious agents or combinations must be defined. Optimal treatment algorithms also
involve minimizing toxicity and maximizing quality of life. And how should
chemotherapy be administered in conjunction with surgery?
It is known, based on animal studies and the “cell kill” hypothesis proposed by
Skipper and co-workers, i.e. a given dose of chemotherapy kills a constant fraction
of tumor cells (Skipper, Schabel & Wilcox, 1964; Wilcox, Griswold, Laster, Schabel &
Skipper, 1965), that cytotoxic drugs are most effective when used for smaller tumors.
Therefore, there is a strong rationale for administering chemotherapy on an
adjuvant basis, after surgical removal of gross disease, for treatment of any
remaining microscopic disease. Indeed, this strategy has been shown effective in
clinical studies, through the pioneering efforts of such investigators as Emil Frei (for
osteosarcoma), Bernard Fisher, Gianni Bonadonna and Umberto Veronesi (for breast
cancer), as well as a number of cooperative groups for colorectal cancer (Bonadonna
et al., 1976; Gastrointestinal Tumor Study Group, 1984; Higgins, Amadeo,
McElhinney, McCaughan, & Keehn, 1984; Jaffe, Frei, Traggis, & Bishop, 1974;
Panettiere et al., 1988; Wolmark et al., 1988). As a result of early successes, the
majority of clinical trials investigating the combination of surgery and systemic
therapy have involved the adjuvant approach.
The rationale for administration of chemotherapy prior to surgery – neoadjuvant
chemotherapy – is very different. Indeed, there is little evidence so far that it improves
survival over adjuvant chemotherapy. In general, neoadjuvant chemotherapy provides
early treatment of systemic and micrometastatic disease. Many patients who have had
X Preface
surgery do not recover sufficiently to receive adjuvant chemotherapy; therefore, giving
it before surgery ensures delivery of systemic therapy to a larger proportion of
individuals. Administration of chemotherapy in the presence of gross, measurable
disease provides information on the sensitivity of a given tumor to a particular
chemotherapeutic regimen, perhaps guiding the choice of agents postoperatively
(when disease is no longer visible). In some instances, downstaging may reduce
disfigurement, dysfunction and morbidity associated with extensive resections, such
as in rectal cancers, vulvar carcinomas and penile carcinomas. Downstaging with
neoadjuvant chemotherapy may also convert an unresectable cancer to a resectable
cancer, such as in colorectal liver metastases. Neoadjuvant chemotherapy may facilitate
selection of candidates for surgery: it may be argued that individuals who have
progression on chemotherapy or who cannot tolerate chemotherapy would not fare well
with aggressive locoregional treatments. Finally, some systemic agents (most notably
angiogenesis inhibitors) are not known to be effective in the adjuvant setting (Kemeny et
al.; Van Cutsem, Lambrechts, Prenen, Jain, & Carmeliet). Therefore, administration prior
to surgery may enhance delivery in conditions where they are effective.
As with any treatment strategy, neoadjuvant chemotherapy also has some potential
disadvantages. If progression occurs, a previously resectable tumor may become
unresectable. Toxicities, including thromboembolic complications and lasting organ
toxicity may increase the risk of subsequent surgery. To detractors, such outcomes
would represent a disadvantage. Moreover, there is the problem of surgical planning
following a complete response. Therefore, there is a need to seriously study the role of
neoadjuvant chemotherapy in each specific instance, where different
chemotherapeutic regimens are utilized for various types of cancer.
In general, data supporting the role of neoadjuvant chemotherapy are more plentiful
for the more common tumors. For example, data related to neoadjuvant chemotherapy
for breast cancer, rectal cancer and metastatic colorectal cancer are accumulating
rapidly, and the role of this treatment approach is slowly becoming elucidated. For
less common tumors, very few data are available to support the role of neoadjuvant
chemotherapy, and research on this treatment approach is just beginning. In such
instances, the experiences related to more common tumor types may inform trials on
these more rare clinical entities.
Interest in neoadjuvant chemotherapy also intensifies with the availability of more
effective systemic agents. For example, in the case of extremity sarcoma, while
neoadjuvant chemotherapy may reduce locoregional recurrence, the paucity of
systemic agents with a high response rate may limit its utility for limb salvage,
limiting its application outside of clinical trials. As systemic agents are developed
that reliably shrink sarcomas, it can be expected that the interest in a neoadjuvant
approach will increase. Certainly, this was the case for gastrointestinal stromal
tumors once imitinib became available; the interest in neoadjuvant chemotherapy
for colorectal liver metastases has similarly surged since the availability of more
effective chemotherapies.
