ONCOLOGY Vol 16 No 9

The Bayer Corporation recently announced that it has teamed up with Us Too! International to offer Continuous Care, a program for advanced prostate cancer patients using the leuprolide acetate implant (Viadur). The program provides appointment reminders, education, support materials, and valuable health coupons.

Patients with advanced colorectal cancer who received the FOLFOX4 regimen (fluorouracil [5-FU], leucovorin, oxaliplatin [Eloxatin]) responded significantly better to treatment, had fewer severe side effects, and lived months longer than did patients

The US Food and Drug Administration (FDA) has approved darbepoetin alfa (Aranesp) for the treatment of chemotherapy-induced anemia in patients with nonmyeloid malignancies. Darbepoetin alfa is a recombinant erythropoietic protein that requires fewer injections than previous treatments used for this indication. The agent maintains its level in the blood approximately three times longer than epoetin alfa (Epogen, Procrit), thus giving health-care providers the ability to treat anemia related to chemotherapy with less-frequent dosing than the current standard of care.

The bisphosphonate zoledronic acid (Zometa) is effective in the treatment of skeletal-related events from bone metastases in prostate cancer patients, according to data presented at the 97th annual meeting of the American Urological Association. Patients with advanced prostate cancer are at high risk for bone complications, including bone pain, pathologic fractures, need for radiation or surgery to bone, and spinal cord compression. This study marks the first time a bisphosphonate has demonstrated efficacy in the treatment of bone metastases in this patient population.

Octreotide (Sandostatin), a somatostatin analog, has a wide range of uses in the management of cancer patients. It is a unique molecule that specifically binds to somatostatin receptor subtype 2. This property of activating the receptor can result in a multitude of physiologic actions (for example, inhibition of synthesis and release of peptides in endocrine and neoplastic cells, antiangiogenesis, antisecretory effect in the gastrointestinal mucosa, anticholecystokinin activity retarding gallbladder motility, and reduction in splanchnic blood flow). In addition, in vitro experiments confirm that octreotide has cytostatic activity against a variety of malignancies. Octreotide is now widely used in the treatment of hormonal syndromes that result from a variety of neuroendocrine and endocrine neoplasms. Its dramatic effect in controlling malignant carcinoid syndrome and hormone-induced diarrhea (for example, from gastrinoma and VIPoma) has been well documented. However, the chronic use of octreotide can result in steatorrhea and gallstone formation.

Medicare’s proposed fee-schedule changes for calendar year 2003 would result in a 3% cut in average payments to oncologists. That reduction is due to an expected 4.4% negative "update" to all physician fees in 2003. The total relative value of the CPT codes used most often by oncologists will actually go up 1% in 2003 because of some positive changes Medicare wants to make in the "practice expense" portion of the relative value formula. However, that increase will not be nearly enough to offset the negative 4.4% update. The negative update could have been worse had Medicare not proposed to change the way it figures a "productivity" element in the Medicare Economic Index (MEI). A measure of inflation in physician inputs, the MEI is itself one of the determinants of the annual Medicare fee update-the higher the MEI, the higher the annual update, or the lower the decrease. The change being proposed by the Centers for Medicare & Medicaid Services raises the estimated 2003 MEI update from 2.3% to 3.0%. Without the productivity change, the update would have been a negative 5.1%. These figures are all preliminary. They will be finalized when Medicare releases a final 2003 fee schedule, probably in late October.

Much progress in the diagnosis and management of well-differentiated neuroendocrine malignancies is evident over the past 2 decades. Initial medical intervention using somatostatin analogs such as octreotide acetate in the immediate and sustained release formulations (Sandostatin and Sandostatin LAR Depot) is standard for the symptomatic stage IV patient.[1,2] Somatostatin analogs provide effective hormonal suppression for carcinoid neoplasm, pancreatic islet cell malignancies, and pituitary adenomas.

In this article, Pandit and Vesole present a focused overview of allogeneic transplantation for multiple myeloma. Additionally, this article addresses the challenges of allogeneic transplantation, including continued relapse and treatment-related toxicity and mortality.

The comprehensive review by Dr. Karen Kelly meticulously outlines the rationale for the study of irinotecan in non-small-cell lung cancer (NSCLC), summarizes results of trials of this agent as monotherapy and as a component of doublet and triplet regimens in previously untreated NSCLC patients, and then reviews its role in previously treated NSCLC patients.

Diarrhea is a common problem in patients receiving pelvic irradiation with concurrent chemotherapy. Virtually all patients develop diarrhea of varying severity during the course of the treatment. The incidence and severity of diarrhea vary with the chemotherapy type and dose, radiotherapy field size, daily fraction size, and total dose of radiation given. Diarrhea (any grade) occurs in 30% to 87% of patients receiving chemotherapy and in 20% to 49% of patients receiving pelvic radiotherapy. The incidence of severe and life-threatening (grade 3/4) diarrhea ranges from 20% to 40% in patients receiving combined chemoradiotherapy.

Multiple myeloma is a multistep malignancy, starting with an indolent phase (monoclonal gammopathy of unknown significance [MGUS] or smoldering myeloma), progressing to overt myeloma (which is typically restricted to the bone marrow), and

Flavopiridol [2-(2-chlorophenyl 5 ,7-dihydroxy-8-[cis-(3-hydroxy-1-methyl-4-piperidinyl)-4H-1-benzopyran-4-one, hydrochloride] is a semisynthetic flavone with a novel structure compared with that of polyhydroxylated flavones, such as quercetin and genistein.[1] It is derived from rohitukine, an alkaloid isolated from the stem bark of Dysoxylum binectariferum, a plant indigenous to India.[2] Originally synthesized and supplied by Hoechst India Limited, flavopiridol is provided to the Division of Cancer Treatment and Diagnosis of the National Cancer Institute (NCI) by Aventis Pharmaceuticals, Inc.

Two of the most important predictors of relapse (and, therefore, survival) in patients with melanoma are the Breslow thickness of the primary melanoma and regional lymph node involvement. Patients with melanomas greater than 4 mm in thickness have approximately a 50% risk of recurrence, and those with lymph node involvement have a 50% to 85% risk of recurrence depending on the number of lymph nodes involved. Thus, a group of patients can be identified who are at high risk of death from melanoma and are, therefore, appropriate candidates for postsurgical adjuvant therapy.

Recommendation for the Management of Patients With Chemotherapy-Induced Diarrhea

Octreotide acetate (Sandostatin), a somatostatin receptor subtype 2 (sst 2)-preferring somatostatin analog, inhibits angiogenesis in a dose-dependent fashion in the chicken chorioallantoic membrane model (CAM) and in the human placental vein angiogenesis model (HPVAM).[1,2] To explain these antiangiogenic effects, sst 2 gene expression in normal (resting) full-thickness human placental vein segments was compared to tissue-matched counterparts that initiated an angiogenic response in culture. Using polymerase chain reaction (PCR) techniques, the sst 2 gene was found to be uniquely up-regulated in the angiogenic vessels, but not present in the tissue-matched resting (nonproliferative) vein segments.

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer death worldwide, causing 549,000 deaths in 2000-10% of all cancer deaths. There are strong etiologic associations with hepatitis C, hepatitis B, alcohol, other causes of cirrhosis, and dietary aflatoxins. The US incidence of HCC is 2.4/100,000 persons/year and rising due to the increased prevalence of hepatitis C.[1] After the current cohort of patients infected with the chronic hepatitis C virus passes, there will likely be a continued increase in the US incidence of HCC due to increasing rates of obesity-related nonalcoholic steatohepatitis, which causes many cases of "cryptogenic cirrhosis."

Surgery has evolved to become the standard of care for a defined subset of patients with hepatic colorectal metastases. Hepatic resections are now well-controlled procedures, with several centers reporting very low perioperative mortality rates.

In this article, Ravikumar and Gallos nicely summarize the current understanding of liver resection for metastases. My comments here will be limited to resection of colorectal metastases, as this is the most common and best characterized of the procedures described.

Dr. Kelly has provided a complete, well-written review of the current status and evolving role of irinotecan (CPT-11, Camptosar) as a cytotoxic agent for patients with non-small-cell lung cancer (NSCLC). Her review clearly demonstrates the value of irinotecan in this patient population and further supports the continued development of this agent in concert with other chemotherapeutic agents, biologically targeted agents, surgery, and/or radiotherapy.

Cancer of the pancreas is the fourth leading cause of cancer death in the United States. Of the 28,000 patients diagnosed each year, more than 95% will die of pancreatic cancer. Therefore, the focus of therapy for most patients is palliative care. In fact, the most active single-agent therapy for advanced disease-gemcitabine (Gemzar)-was first compared to fluorouracil (5-FU) with relief of disease symptoms as a primary end point. However, the survival with gemcitabine remains approximately 6 months for advanced disease, and no new agent, either alone or in combination, has exceeded this time frame in phase III study.

Normal and hyperplastic prostate glandular epithelium does not express somatostatin receptors. Neuroendocrine prostatic cells contain bioactive secretory products such as chromogranin A, serotonin, and neuron-specific enolase. The stromal smooth muscle cells around glandular epithelium and ganglion cells of the prostatic plexus are positive for somatostatin subtype 2 receptors (sst 2).[1] In prostate cancer, however, there is nonhomogeneous distribution of sst 1. In the peritumoral veins of prostate cancer, sst 2 receptors were found by Reubi et al in 14 of 27 samples.[2]

Gastroenteropancreatic tumors, although relatively rare, present management problems that may last many years, in comparison with the usually more aggressive adenocarcinomas whose management may encompass a far briefer span of time. In general, 50% of such tumors are insulinomas, while gastrinomas comprise 25%, and nonfunctional tumors 20% VIPomas and glucagonomas are the predominant lesions of the remaining 5%. Clinical diagnosis is usually made on the presence of the classical symptom complex. In uncertain circumstances or covert presentations, the critical diagnostic biochemical test is plasma chromogranin A as well as measurement of the specific peptide.

In this article, we present current surgical perspectives on the management of liver metastases, with a focus on state-of-the-art resection, by drawing on clinical data provided in the medical literature. Metastases from

Lung cancer remains the primary cause of cancer-related death in both men and women in the United States. Chemotherapy has been shown to provide a survival benefit in patients with advanced non-small-cell lung cancer (NSCLC), and current regimens have produced median survivals of approximately 8 months and 1-year survival rates of 30% to 35% in patients with stage IIIB and IV disease. Nevertheless, there remains room for improvement. Irinotecan (CPT-11, Camptosar) has demonstrated efficacy in the treatment of small-cell lung cancer (SCLC). It also appears to have promising activity in advanced NSCLC, producing overall response rates of up to 32%. Combinations of irinotecan and cisplatin or carboplatin (Paraplatin) have resulted in overall response rates of 25% to 56% in phase II and III studies in patients with advanced disease, with median survivals ranging from 9 to 13 months and 1-year survival rates of 33% to 58%. Current irinotecan-based doublet and triplet regimens appear to produce promising response rates with manageable toxicities. In addition, irinotecan has demonstrated potential as a radiosensitizing agent and is currently being evaluated in several trials of combined-modality therapy in patients with locally advanced NSCLC. Early trials of irinotecan in combination with cisplatin or carboplatin along with radiation therapy have reported overall response rates of 60% to 67%. The approach appears to have potential and warrants further study. [ONCOLOGY 16:1153-1168, 2002]

An estimated 14,600 new cases of multiple myeloma will be diagnosed in the United States in 2002. Multiple myeloma remains an incurable disease despite significant improvements in complete response rates and overall

This second installment on prostate specific antigen (PSA) as a marker of disease activity and cancer cell viability in prostate cancer focuses on its role in monitoring the effects of a variety of therapies at different stages of the disease. In addition, the authors propose guidelines for studying the efficacy of new treatments in this setting.

As a tumor marker, prostate specific antigen (PSA) has revolutionized the detection and management of adenocarcinoma of the prostate. From its discovery in the early 1970s to its application in the 1980s and finally widespread use in the 1990s, PSA has profoundly affected the way in which we treat prostate cancer. Many researchers in basic science and clinical practice have helped to create the PSA story, and the authors of this manuscript have made major contributions to our understanding of PSA as a tumor marker.

Despite the impact of prostate-specific antigen (PSA) testing on the detection and management of prostate cancer, controversy about its usefulness as a marker of disease activity continues. This review, based on a

Despite more than 2 decades of active clinical study, the use of interferon as adjuvant therapy for high-risk melanoma remains controversial. The controversy has centered on dose, schedule, and toxicity of treatment. Agarwala and Kirkwood superbly summarize the clinical studies to date and highlight many of the salient issues relevant to clinicians.

Melanoma is almost 100% curable when diagnosed early, but when metastatic to distant organs, it is associated with a poor survival. The interferons have shown the most promise in the treatment of melanoma and interferon