ONCOLOGY Vol 11 No 9 | Oncology

AIDS Rates in the US, 1996

September 01, 1997

The map shown in Figure 1 provides the annual rates of acquired immunodeficiency syndrome (AIDS) per 100,000 population, by state of residence from January through December 1996. Table 1 lists the metropolitan areas with the 50

Multidisciplinary Evaluation and Treatment: Evolution to Standard Clinical Practice

September 01, 1997

Combined-modality therapy integrating chemotherapy with radiotherapy and/or surgery is playing an increasing role in the day-to-day management of a wide variety of solid tumors. No longer is this approach solely a clinical research tool. In fact, in

Melanoma Surgical Practice Guidelines

September 01, 1997

The Society of Surgical Oncology surgical practice guidelines focus on the signs and symptoms of primary cancer, timely evaluation of the symptomatic patient, appropriate preoperative evaluation for extent of disease, and role of the surgeon in

The Radiologic Appearance of Lung Cancer

September 01, 1997

It should be noted that the most common presentation of asymptomatic lung cancer is indeed a solitary pulmonary nodule (SPN), but for most symptomatic lung cancers the nodule is at least 3 cm in diameter at the time of initial diagnosis. The author does a good job of providing documentation to refute one of his critical hypotheses, which indicates that "neoplasm can often be strongly suspected or excluded based on the radiologic characteristics of the single pulmonary nodule."

UFT: East Meets West in Drug Development

September 02, 1997

Although the combination of uracil and tegafur (UFT) has been available commercially in Japan since 1984 and is one of the most extensively prescribed antineoplastic agents in that country, few physicians outside Japan have knowledge of and

Soft-Tissue Sarcoma Surgical Practice Guidelines

September 01, 1997

The Society of Surgical Oncology surgical practice guidelines focus on the signs and symptoms of primary cancer, timely evaluation of the symptomatic patient, appropriate preoperative evaluation for extent of disease, and role of the surgeon in diagnosis and treatment. Separate sections on adjuvant therapy, follow-up programs, or management of recurrent cancer have been intentionally omitted. Where appropriate, perioperative adjuvant combined-modality therapy is discussed under surgical management. Each guideline is presented in minimal outline form as a delineation of therapeutic options.

Society of Surgical Oncology Practice Guidelines: Introductory Remarks

September 01, 1997

Thousands of practice guidelines/practice parameters have been published by various professional organizations. The American Medical Association,[1] American College of Physicians,[2,3] and others[4-6] have written extensively about

Prostate-Specific Antigen: What’s New in 1997

September 01, 1997

In this article, the authors have done an excellent job in reviewing recent findings regarding prostate-specific antigen (PSA) and other methods for the early detection of prostate cancer. This is a fast-moving field, with new results being reported on a weekly basis. Indeed, it is an exciting time to be conducting research in prostate cancer. At the same time, however, it is far too easy to lose sight of some of the basic principles by which we should judge evidence to make research or clinical decisions. Specifically, there are hard-learned epidemiologic lessons about which we need to constantly remind ourselves.

Prostate-Specific Antigen: What’s New in 1997

September 01, 1997

This review of prostate-specific antigen (PSA) by Pannek and Partin, two experts in the prostate marker field, comes at a very good time-a point at which great changes are occurring after a relatively long period of stability. I expect that this trend will continue. Moreover, given the rapid developments occurring in this area, some of the statements made in both the review and my commentary will probably need to be modified within the next 12 months, with further revisions necessary thereafter.

Combined-Modality Therapy of Locally Advanced Non-Small-Cell Lung Cancer

September 01, 1997

Treatment of patients with unresectable stage IIIA and IIIB non-small-cell lung cancer with conventionally-fractionated radiation therapy (ie, total doses of 50 to 60 Gy, using one fraction per day), which was standard

Rationale for Phase I Study of UFT Plus Leucovorin and Oral JM-216

September 02, 1997

Both cisplatin (Platinol) and fluorouracil (5-FU) have demonstrated single-agent clinical efficacy in a variety of solid neoplasms. The combination of these agents has revealed synergistic cytotoxicity in models in vitro and in vivo, which may explain the clinical effectiveness of 5-FU-cisplatin regimens. UFT (tegafur and uracil) and bis-aceto-ammine-dichloro-cyclohexyl-amine platinum (IV) (JM-216) are novel oral analogues of 5-FU and cisplatin, respectively. In preclinical models, JM-216 has demonstrated equivalent cytotoxicity to cisplatin, while phase I trials suggest its dose-limiting toxicity is myelosuppression. In contrast to cisplatin, JM-216 has not demonstrated significant neurotoxicity or nephrotoxicity. UFT has been used extensively in Japan, where phase II data suggest disease response rates similar to single-agent 5-FU in colorectal, gastric, and breast carcinomas. Combination studies of prolonged administration UFT and single-dose cisplatin have shown efficacy, but also significant hematologic toxicity. We propose a phase I study of UFT and JM-216 administered daily over 14 consecutive days with leucovorin (90 mg/d). Ease of administration and continuous drug exposure are potential advantages of this regimen. Several disease specific investigations may be warranted given demonstrated feasibility in this phase I study.[ONCOLOGY 11(Suppl 10):26-29, 1997]

Postoperative Adjuvant Chemotherapy for Non-Small-Cell Lung Cancer

September 02, 1997

Given that no therapeutic methods of postoperative adjuvant chemotherapy for non-small-cell lung cancer have been established, we selected UFT (tegafur and uracil) for investigation because UFT is less injurious to the host

UFT in Gastric Cancer: Current Status and Future Developments

September 02, 1997

Despite recent progress in surgery and chemotherapy, advanced gastric cancer carries a poor prognosis. Although several antitumor agents have some clinical activity, responses are usually of short duration and fail to

Oral UFT and Leucovorin in Patients With Advanced Gastric Carcinoma

September 02, 1997

Thirty-nine patients with locally advanced or metastatic gastric carcinoma received oral UFT (tegafur and uracil) plus leucovorin. Treatment consisted of UFT 360 mg/m2/day plus leucovorin 25 mg/m2/day, given orally in divided

Oral UFT Plus Leucovorin in Patients With Relapsed or Refractory Colorectal Cancer

September 02, 1997

Therapeutic options for patients with advanced colorectal cancer who have failed treatment with fluorouracil (5-FU) are limited. Responses have been reported in this setting with a protracted venous infusion of 5-FU. Daily oral therapy with tegafur and uracil (UFT) plus leucovorin (LV) has the potential to mimic the pharmacology of continuous infusion 5-FU. Therefore, we undertook a phase II study of a 28-day schedule of a combination chemotherapy regimen containing oral UFT/leucovorin in patients with measurable metastatic colorectal cancer who had failed treatment with bolus 5-FU. In addition, we sought to determine whether coadministration of UFT and leucovorin alters the bioavailability of these agents. In a pretreatment phase, each patient underwent sequential pharmacokinetic sampling following a single dose of UFT alone, leucovorin alone, and the combination of UFT plus leucovorin. The preliminary results of this trial suggest that tegafur pharmacokinetics are not affected by coadministration of leucovorin and that folate pharmacokinetics are not affected by UFT. [ONCOLOGY 11(Suppl 10):22-25, 1997]

Postoperative Adjuvant Chemotherapy With Mitomycin C and UFT for Rectal Cancer

September 02, 1997

To evaluate the significance of postoperative adjuvant chemotherapy using mitomycin C (MMC) and UFT (tegafur and uracil) in combination, the Japanese Foundation for Multidisciplinary Treatment of Cancer conducted a prospective randomized controlled trial with 834 patients who had undergone curative resection for rectal cancer (T3 or T4 tumors and/or N1, N2, or N3 disease). The patients were randomly allocated to a treatment group (MMC/UFT, 416 patients) and a control group (surgery only, 418 patients). For patients in the treatment group, 20 mg of MMC was sprinkled on the operating field upon completion of surgery. MMC was intravenously injected at 6 mg/m2 on day 7, and then each month after surgery for 6 months. UFT was administered orally at 400 mg/day for 1 year. Although no difference was observed in the 5-year survival rate between the two groups, the 5-year disease-free survival rate in the MMC/UFT group was 69.1%, which was significantly higher than in the control group (59.3%, P = .005). The 5-year cumulative local recurrence rate was significantly lower in the MMC/UFT group (11.6%) than in the control group (19.0%) (P = .0071). We conclude that the adjuvant use of long-term oral UFT and intermittent intravenous MMC improves the disease-free survival rate of patients with curatively resected rectal cancer. [ONCOLOGY 11(Suppl 10):40-43, 1997]

UFT Plus Leucovorin in Advanced Hepatobiliary Tumors and Pancreatic Adenocarcinomas

September 02, 1997

UFT (tegafur and uracil) has been studied extensively in Japan, with documented efficacy in hepatobiliary and pancreatic cancer. In the United States, UFT with or without leucovorin has not undergone phase II testing in

Combined-Modality Treatment of Esophageal Cancer

September 01, 1997

The use of chemotherapy and radiotherapy prior to surgery for patients with potentially resectable esophageal carcinoma has been investigated since the late 1970s, with trials yielding response rates approaching 50%.

Experience With UFT in Japan

September 02, 1997

The selective antineoplastic effect of tegafur and uracil (UFT) is attributed to its preferential enhancement of fluorouracil concentration in tumor tissues compared with that in normal tissues. The result of this effect is evident in the clinical benefit and lower toxicity associated with UFT compared with other fluorinated pyrimidines. Beginning with preclinical studies in the 1980s, significant therapeutic advantages of UFT have been reported in numerous trials conducted in Japan, including phase I dose-finding studies, phase II multicenter studies, comparative studies, and combination-chemotherapy studies. In phase II studies conducted at 211 institutions, for example, it was shown that the response rate was over 30% in patients with head/neck, bladder, or breast cancer, and the survival rate was superior to that previously reported in Japanese studies. Two comparative studies suggested that UFT was more effective than single-agent tegafur, and a number of combination-chemotherapy studies have shown that it has an advantage in terms of toxicity, response, and/or survival. UFT is also useful for postoperative adjuvant therapy, as well as therapy for advanced disease in a variety of neoplasms. UFT holds considerable promise and future trials should continue the evaluation and refinement of its role in the treatment of cancer.[ONCOLOGY 11(Suppl 10):30-34, 1997]

Future Directions in the Adjuvant Treatment of Colon Cancer

September 02, 1997

Adjuvant chemotherapy has been shown to alter the natural history of patients with resected colon cancer. Two regimens (fluorouracil [5-FU] plus levamisole (Ergamisol) and 5-FU plus leucovorin) have been found most

UFT Plus Cisplatin for Advanced Gastric Cancer

September 02, 1997

In a laboratory study using an experimental peritoneum model of gastrointestinal cancer, the UFTP [tegafur and uracil (UFT) plus cisplatin] regimen was shown to provide a survival benefit compared with the UFTM (UFT plus

Phase I and Pharmacokinetic Evaluations of UFT Plus Oral Leucovorin

September 02, 1997

The phase I development program of tegafur and uracil (UFT) in the United States has included evaluation of the drug as a single agent and subsequent studies of its biochemical modulation by oral leucovorin. Phase I trials of single-agent UFT examined both a 5-day schedule repeated every 21 days and a 28-day schedule repeated every 35 days. In all of the trials the total dose was divided by three and administered three times daily at 8-hour intervals. Like intravenous schedules of fluorouracil (5-FU), UFT has schedule-dependent toxicity, with granulocytopenia being the dose-limiting toxicity for the 5-day regimen and diarrhea being the dose-limiting toxicity for the 28-day regimen. The suggested phase II doses for UFT administered without leucovorin were 800 mg/m2/day for the 5-day schedule and 360 mg/m2/day for the 28-day schedule. Subsequent phase I studies combining UFT with oral leucovorin used a 28-day schedule repeated every 35 days. Diarrhea was the dose-limiting toxicity, and the recommended phase II dose was UFT, 300 mg/m2/day, plus leucovorin, 90 mg/day. Pharmacokinetic evaluation showed that single-dose UFT results in maximum plasma levels and an area under the concentration-time curve that increased with escalating UFT doses. In addition, 5-FU levels were detectable throughout the 28-day dosing period; however, there was no evidence of significant accumulation of uracil, tegafur, or 5-FU. The administration of leucovorin in this trial provided continuous exposure of d,l-leucovorin and 5-methyltetrahydrofolate with little variation between doses or days.[ONCOLOGY 11(Suppl 10):35-39, 1997]

Preoperative Combined Oral UFT Plus Leucovorin and Radiation Therapy for Rectal Cancer

September 02, 1997

Several trials performed in the United States and Europe have demonstrated the efficacy of UFT (uracil and tegafur in a 4:1 molar combination) with oral leucovorin in the treatment of several tumor types, but particularly

UFT Plus Cisplatin in Advanced Non-Small-Cell Lung Cancer: Interim Analysis of 67 Patients

September 02, 1997

A single-institution phase II study indicated that combination chemotherapy using UFT (tegafur and uracil) plus cisplatin (Platinol) in patients with non-small-cell lung cancer was active with less host toxicity than other cisplatin-

Scientific Basis for the Combination of Tegafur With Uracil

September 02, 1997

Fujii et al reported that Uracil potentiated the antitumor activity of fluorouracil (5-FU) and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur). This effect was due to inhibition of the degradation of 5-FU, yet the phosphorylation of 5-FU was unaffected. The molar ratio of tegafur and uracil was 1:4, a combination that has since been widely prescribed in Japan for the treatment of cancer patients. We present here our experimental and clinical results when investigating the antineoplastic effects of this combination of drugs-known as UFT-and provide evidence that UFT is an effective treatment for patients with cancer. [ONCOLOGY 11(Suppl 10):14-21, 1997]

UFT in Combination as Adjuvant Therapy for Breast Cancer

September 02, 1997

Between 1989 and 1993, 409 evaluable patients with breast cancer have been treated with tegafur and uracil (UFT) in an adjuvant setting in two different trials. Data from both trials were reviewed in December 1995 after a

UFT Plus Leucovorin vs 5-FU Plus Leucovorin for Metastatic Colorectal Cancer

September 02, 1997

An open-label, randomized phase III trial has been established to compare the efficacy and safety profile of tegafur and uracil (UFT) plus leucovorin with fluorouracil (5-FU) plus leucovorin as first-line chemotherapy for

Metastatic Breast Cancer: Treatment With Fluorouracil-Based Combinations

September 02, 1997

During the 1990s, one in nine women in the western world will be diagnosed with breast cancer, and more than 58,000 will die of the disease each year in Europe alone. Recent changes in the primary therapy of operable

Prostate-Specific Antigen: What’s New in 1997

September 01, 1997

When used alone, prostate-specific antigen (PSA) is not sufficiently sensitive or specific to consider it an ideal tool for the early detection or staging of prostate cancer. To optimize the use of PSA, the concepts of PSA velocity,

Lumpectomy With and Without Radiation for Early-Stage Breast Cancer and DCIS

September 01, 1997

Breast-conserving therapy with lumpectomy and breast irradiation is an accepted standard treatment for patients with early-stage invasive breast cancer or ductal carcinoma in situ (DCIS). For both diseases, investigators have tried to identify subgroups of patients who can be "safely" treated with lumpectomy without radiation. Some data suggest that it may be reasonable to omit radiation therapy in patients with small, low-grade invasive or noninvasive tumors and/or in "elderly" patients. Additional studies are needed to better identify criteria to prospectively select appropriate patients for treatment with lumpectomy alone. [ONCOLOGY 11(9):1361-1374, 1997]

Commentary (Abrams): Lumpectomy With and Without Radiation for Early-Stage Breast Cancer and DCIS

September 01, 1997

To irradiate or not to irradiate, that is the question posed by Marks and Prosnitz for women with early invasive breast cancer or ductal carcinoma in situ (DCIS) undergoing breast conservation therapy (BCT). Due in large part to mammography, there has been in the 1990s a significant increase in the percentage of women presenting with stage 0 (DCIS) and stage I breast cancer, as recorded by the Surveillance, Epidemiology and End-Results Program of the National Cancer Institute (NCI). The generally excellent outcome of these tumors with current therapy has focused research efforts on studies directed at improving quality of life and minimizing the side-effects and expense of local therapy. In this regard, Marks/Prosnitz present a concise and balanced summary of results from randomized and non-randomized clinical trials, and develop a rationale for current treatment recommendations and future studies regarding the role of breast irradiation (RT).

The Radiologic Appearance of Lung Cancer

September 01, 1997

A solitary pulmonary nodule (SPN) is the most common radiographic presentation of lung cancer. The imaging characteristics of solitary pulmonary nodules are described and illustrated. The appearance and implications of

Commentary (Giles/Kantarjian): Biology and Treatment of Chronic Myelogenous Leukemia

September 01, 1997

Drs. Enright and McGlave succinctly review the biology of chronic myelogenous leukemia (CML) and highlight the therapeutic role of allogeneic stem-cell transplantation. Two points, however, warrant further discussion. The first is that a regimen containing interferon-alfa (Intron A, Roferon-A) is optimal front-line therapy for the great majority of CML patients.[1] The second is that use of an interferon-alfa-based regimen prior to allogeneic stem-cell transplantation does not adversely affect post-transplant mortality, morbidity, or anti-CML efficacy.