ONCOLOGY Vol 20 No 6

FDA Clears Extended Dosing of Darbepoetin for Chemotherapy-Induced Anemia

Rising CA-125 levels are a cause for concern among ovarian cancer

Orphan Drug Status Granted to Sorafenib for Liver Cancer

NCI Director Nominated as New FDA Commissioner

It's been an interesting time for those of us who treat patients with lung cancer. Over the past few years, non-small-cell lung cancer (NSCLC) has been a target for the numerous companies developing agents that inhibit receptors, growth factors, signaling molecules, and genes involved in tumor growth and development. The "biologic-targeted" approach to treatment is still in its infancy, but it has already given us great expectations, some surprises, some disappointments, and, ultimately, satisfaction that we now have a nonchemotherapeutic option.

Drugs approved by the US Food and Drug Administration (FDA) must demonstrate substantial evidence of efficacy from adequate and well-controlled trials and be safe for their intended use. A 1962 amendment to that Act codifies the efficacy requirement. Guidance promulgated in the 1980s indicated that efficacy should represent a "clinical benefit" demonstrated by prolongation of life, better life, or effect on an established surrogate for at least one of these. Direct clinical benefit assessments have included improvements in survival, physical functioning, or tumor-related symptoms.

New Report on Survivorship Finds Minorities and Poor Least Likely to Remain Cancer-Free

STAR Trial Shows Raloxifene to Be as Effective as Tamoxifen in Preventing Invasive Breast Cancer

Carcinoembryonic antigen (CEA) monitoring in patients with stage I-IV colorectal cancer has been, and remains, a controversial issue in oncology practice. Recommendations vary from bimonthly monitoring to no monitoring in the surveillance setting (for stage I-III disease). In the metastatic setting, there are no clear guidelines for CEA follow-up, although continued monitoring in such patients is common in the oncology community. This manuscript reviews the accuracy of CEA testing, its value as a prognostic indicator, and its role in surveillance and response assessment. The limitations of the test in the adjuvant and metastatic settings are illustrated through several case reports from the Colorectal Oncology Clinic at Roswell Park Cancer Institute. Guidelines for CEA monitoring are provided, based on a detailed literature review and institutional experience.

Carcinoembryonic antigen (CEA) monitoring in patients with stage I-IV colorectal cancer has been, and remains, a controversial issue in oncology practice. Recommendations vary from bimonthly monitoring to no monitoring in the surveillance setting (for stage I-III disease). In the metastatic setting, there are no clear guidelines for CEA follow-up, although continued monitoring in such patients is common in the oncology community. This manuscript reviews the accuracy of CEA testing, its value as a prognostic indicator, and its role in surveillance and response assessment. The limitations of the test in the adjuvant and metastatic settings are illustrated through several case reports from the Colorectal Oncology Clinic at Roswell Park Cancer Institute. Guidelines for CEA monitoring are provided, based on a detailed literature review and institutional experience.

The manuscripts that comprise this supplement "Defining Clinical Endpoints in Renal Cell Carcinoma" are presented by six leading international clinical and basic investigators, and are derived from their presentations at the roundtable discussion, "Defining Clinical Endpoints in Renal Cell Carcinoma," which took place in Chicago on October 21, 2005, sponsored by Bayer HealthCare.

Twenty years ago, antiestrogen therapy with tamoxifen played only a secondary role in breast cancer care. All hopes to cure metastatic breast cancer were still pinned on either the discovery of new cytotoxic drugs or a dose-dense combination of available cytotoxic drugs with bone marrow transplantation. A similar strategy with combination chemotherapy was employed as an adjuvant for primary breast cancer. Simply stated, the goal was to kill the cancer with nonspecific cytotoxic drugs while keeping the patient alive with supportive care. However, medical research does not travel in straight lines, and an alternative approach emerged to solve the problem of controlling tumor growth with minimal side effects: targeted therapy. The approach of using long-term antihormone therapy to control early-stage breast cancer growth would revolutionize cancer care by targeting the tumor estrogen receptor (ER). The success of the strategy would contribute to a decrease in the national mortality figures for breast cancer. More importantly, translational research that targeted the tumor ER with a range of new antiestrogenic drugs would presage the current fashion of blocking survival pathways for the tumor by developing novel targeted treatments. But a surprise was in store when the pharmacology of "antiestrogens" was studied in detail: The nonsteroidal "antiestrogens" are selective ER modulators—ie, they are antiestrogens in the breast, estrogens in the bone—and they lower circulating cholesterol levels. This knowledge would establish a practical approach to breast cancer chemoprevention for women at high risk (tamoxifen) and low risk (raloxifene).

Twenty years ago, antiestrogen therapy with tamoxifen played only a secondary role in breast cancer care. All hopes to cure metastatic breast cancer were still pinned on either the discovery of new cytotoxic drugs or a dose-dense combination of available cytotoxic drugs with bone marrow transplantation. A similar strategy with combination chemotherapy was employed as an adjuvant for primary breast cancer. Simply stated, the goal was to kill the cancer with nonspecific cytotoxic drugs while keeping the patient alive with supportive care. However, medical research does not travel in straight lines, and an alternative approach emerged to solve the problem of controlling tumor growth with minimal side effects: targeted therapy. The approach of using long-term antihormone therapy to control early-stage breast cancer growth would revolutionize cancer care by targeting the tumor estrogen receptor (ER). The success of the strategy would contribute to a decrease in the national mortality figures for breast cancer. More importantly, translational research that targeted the tumor ER with a range of new antiestrogenic drugs would presage the current fashion of blocking survival pathways for the tumor by developing novel targeted treatments. But a surprise was in store when the pharmacology of "antiestrogens" was studied in detail: The nonsteroidal "antiestrogens" are selective ER modulators—ie, they are antiestrogens in the breast, estrogens in the bone—and they lower circulating cholesterol levels. This knowledge would establish a practical approach to breast cancer chemoprevention for women at high risk (tamoxifen) and low risk (raloxifene).

Twenty years ago, antiestrogen therapy with tamoxifen played only a secondary role in breast cancer care. All hopes to cure metastatic breast cancer were still pinned on either the discovery of new cytotoxic drugs or a dose-dense combination of available cytotoxic drugs with bone marrow transplantation. A similar strategy with combination chemotherapy was employed as an adjuvant for primary breast cancer. Simply stated, the goal was to kill the cancer with nonspecific cytotoxic drugs while keeping the patient alive with supportive care. However, medical research does not travel in straight lines, and an alternative approach emerged to solve the problem of controlling tumor growth with minimal side effects: targeted therapy. The approach of using long-term antihormone therapy to control early-stage breast cancer growth would revolutionize cancer care by targeting the tumor estrogen receptor (ER). The success of the strategy would contribute to a decrease in the national mortality figures for breast cancer. More importantly, translational research that targeted the tumor ER with a range of new antiestrogenic drugs would presage the current fashion of blocking survival pathways for the tumor by developing novel targeted treatments. But a surprise was in store when the pharmacology of "antiestrogens" was studied in detail: The nonsteroidal "antiestrogens" are selective ER modulators—ie, they are antiestrogens in the breast, estrogens in the bone—and they lower circulating cholesterol levels. This knowledge would establish a practical approach to breast cancer chemoprevention for women at high risk (tamoxifen) and low risk (raloxifene).

Carcinoembryonic antigen (CEA) monitoring in patients with stage I-IV colorectal cancer has been, and remains, a controversial issue in oncology practice. Recommendations vary from bimonthly monitoring to no monitoring in the surveillance setting (for stage I-III disease). In the metastatic setting, there are no clear guidelines for CEA follow-up, although continued monitoring in such patients is common in the oncology community. This manuscript reviews the accuracy of CEA testing, its value as a prognostic indicator, and its role in surveillance and response assessment. The limitations of the test in the adjuvant and metastatic settings are illustrated through several case reports from the Colorectal Oncology Clinic at Roswell Park Cancer Institute. Guidelines for CEA monitoring are provided, based on a detailed literature review and institutional experience.

Brain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.

Brain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.

Brain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.