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Adjuvant Therapy for Gastric Carcinoma: Closing out the Century

Gastric cancer is often advanced and unresectable at diagnosis. Even when a curative resection is possible, the 5-year survival rate for patients with T2 or higher tumors is less than 50%. Survival rates are even lower if lymph node metastases are present at surgery. Many phase III trials of adjuvant therapy have been conducted around the world during the past 4 decades, but their interpretation varies in the East and West. In the West, postoperative treatment modalities have not proven to be superior to postsurgical observation alone. Thus, at present, the routine use of postoperative therapy should be discouraged. In the Orient, however, routine use of postoperative chemotherapy and/or immunotherapy is common after a surgical procedure. Further investigations that correlate treatment response with molecular markers are needed. Improved clinical trial designs, including better preoperative staging, standardized surgical techniques, inclusion of adequate numbers of patients, and the continued use of a surgery-alone control group, are essential. In addition, the incorporation of newer active agents, radiotherapy, and new strategies, such as preoperative therapy and selection of patients based on tumor biology, would result in much-needed advances. Less toxic approaches with novel mechanisms of action, such as antiangiogenesis therapy, tumor vaccines, monoclonal antibodies, and matrix metalloproteinase inhibitors, also hold promise. [ONCOLOGY 13(11):1485-1494, 1999]

Latest Article

New Therapeutic Options for Chronic Lymphocytic Leukemia

For decades, initial therapy for chronic lymphocytic leukemia (CLL) consisted of alkylators such as chlorambucil (Leukeran). The introduction of nucleoside analogs such as fludarabine and monoclonal antibodies such as rituximab (Rituxan) markedly changed the initial therapy of CLL, particularly in the United States. Fludarabine and combination regimens such as fludarabine/cyclophosphamide (FC) have achieved higher complete response (CR) rates and progression-free survival (PFS) than chlorambucil in previously untreated CLL, but long-term overall survival has not improved, due to concurrent improvement in salvage therapy of relapsed CLL patients. Upfront chemoimmunotherapy regimens such as fludarabine/rituximab (FR) and fludarabine/cyclophosphamide/rituximab (FCR) have similarly improved CR rates and PFS in previously untreated CLL patients, but it is unclear whether overall survival is improved. Advances in cytogenetic analysis and other biologic prognostic factors have greatly enhanced clinicians' ability to risk-stratify newly diagnosed CLL patients, and knowledge of such prognostic factors is necessary to properly interpret results of clinical treatment studies. The choice of initial therapy for an individual patient should depend upon the patient's age and medical condition, cytogenetic and other prognostic factors, and whether the goal of therapy is maximization of CR and PFS or palliation of symptoms with minimal toxicity.

Latest Article

Choices in the Treatment of Cutaneous T-Cell Lymphoma

Mycosis fungoides is responsive to treatment in the early stages; patients have a long duration of survival but are rarely cured of the disease. Therefore, patients require long-term, sequential therapies with as little toxicity as possible. In the early stages, skin-directed therapies, such as psoralen plus ultraviolet A in combination with retinoids or interferon, generally produce good, long-term responses. Once the disease progresses, systemic agents such as cytokines and retinoids are introduced. The cytokines provide a rational treatment approach for cutaneous T-cell lymphoma (CTCL) and produce good, long-lasting responses with few immunosuppressant effects. Denileukin diftitox (Ontak) has also been shown to produce good treatment effects, and its toxic effects can usually be controlled using prophylactic therapies. The synthetic retinoid bexarotene (Targretin) is taken orally and produces high response rates in CTCL, with a good long-term tolerability profile. Conventional systemic chemotherapies produce rapid responses and high response rates in CTCL, but these are generally of short duration and accompanied by myelosuppression and immunosuppression. Current treatment strategies therefore consist of the use of initial skin-directed therapies, with the addition of low-toxicity systemic biologic agents as the disease progresses; patients who do not respond to biologic agents should then receive conventional chemotherapies, starting with single agents and progressing to combination therapies.

Latest Article

GM-CSF and Low-Dose Cytosine Arabinoside in High-Risk, Elderly Patients With AML or MDS

Priming of leukemic cells with cytokines may enhance the efficacy of cell-cycle chemotherapy. In this study, we utilized these synergistic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]), hydroxyurea, and low-dose cytosine arabinoside to treat elderly patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). In a single-institution, retrospective study, we evaluated 94 treatments with concomitant hydroxyurea, cytosine arabinoside, and GM-CSF between the years of 1997 and 2003 in high-risk elderly patients with AML or MDS. A total of 80% of patients received all of the GM-CSF doses; 78% of patients received all of the cytosine arabinoside doses. Adverse events were minimal. No patient developed mucositis or alopecia. The most common adverse event was neutropenic fever, which was noted in 57% of patients. Twenty-one percent of patients remained neutropenic after treatment until death or relapse. Sixty-eight percent of patients reached an absolute neutrophil count of greater than 1,000 μL in a median of 33.5 days. Our data show an overall response rate of 52%, with a complete response rate of 39% and a partial response rate of 13%. Overall, our study showed that low-dose cytosine arabinoside given by continuous infusion together with continuous infusion GM-CSF and hydroxyurea was well-tolerated and effective in treating elderly AML and MDS patients who were not eligible for standard induction therapy.

Latest Article

Cisplatin, Fluorouracil, Celecoxib, and RT in Resectable Esophageal Cancer: Preliminary Results

Esophageal cancer frequently expresses cyclooxygenase-2 (COX-2)enzyme. In preclinical studies, COX-2 inhibition results in decreasedcell proliferation and potentiation of chemotherapy and radiation. Wereport preliminary results of a phase II study conducted by the HoosierOncology Group in patients with potentially resectable esophageal cancer.All patients received cisplatin at 75 mg/m2 given on days 1 and 29and fluorouracil (5-FU) at 1,000 mg/m2 on days 1 to 4 and 29 to 32with radiation (50.4 Gy beginning on day 1). Celecoxib (Celebrex) wasadministered at 200 mg orally twice daily beginning on day 1 untilsurgery and then at 400 mg orally twice daily until disease progressionor unexpected toxicities, or for a maximum of 5 years. Esophagectomywas performed 4 to 6 weeks after completion of chemoradiation. Theprimary study end point was pathologic complete response (pCR). Secondaryend points included response rate, toxicity, overall survival, andcorrelation between COX-2 expression and pCR. Thirty-one patientswere enrolled from March 2001 to July 2002. Respective grade 3/4 toxicitieswere experienced by 58%/19% of patients, and consisted of granulocytopenia(16%), nausea/vomiting (16%), esophagitis (10%), dehydration(10%), stomatitis (6%), and diarrhea (3%). Seven patients (24%)required initiation of enteral feedings. There have been seven deathsso far, resulting from postoperative complications (2), pulmonary embolism(1), pneumonia (1), and progressive disease (3). Of the 22 patients(71%) who underwent surgery, 5 had pCR (22%). We concludethat the addition of celecoxib to chemoradiation is well tolerated. ThepCR rate of 22% in this study is similar to that reported with the use ofpreoperative chemoradiation in other trials. Further follow-up is necessaryto assess the impact of maintenance therapy with celecoxib onoverall survival.