International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation.

Purpose: To provide an update on recent advances in the management of patients with multiple myeloma who are not eligible for autologous stem-cell transplantation.

Methods: A comprehensive review of the literature on diagnostic criteria is provided, and treatment options and management of adverse events are summarized.

Results: Patients with symptomatic disease and organ damage (ie, hypercalcemia, renal failure, anemia, or bone lesions) require immediate treatment.

Inhibition of epidermal growth factor receptor and symptom improvement in advanced non-small cell lung cancer.

The majority of patients with non-small cell lung cancer (NSCLC) are not candidates for curative resection because of advanced disease at the time of diagnosis. Systemic chemotherapy has been employed with modest success to provide symptom relief and prolonged survival for patients with this incurable disease. Any benefit derived from chemotherapy in this palliative setting must be balanced against the substantial toxicity associated with cytotoxic drugs.

Gemcitabine-containing regimens vs others in first-line treatment of NSCLC.

Standard first-line chemotherapy regimens in advanced non-small-cell lung cancer (NSCLC) include carboplatin (Paraplatin)/paclitaxel, cisplatin/docetaxel (Taxotere), cisplatin/gemcitabine (Gemzar), and cisplatin/vinorelbine (Navelbine). An informal meta-analysis of 13 randomized trials of these regimens in NSCLC indicates no marked differences in terms of response rates or survival, but toxicity advantages with cisplatin/gemcitabine and cisplatin/vinorelbine regimens. An informal meta-analysis to assess the feasibility of substituting carboplatin for cisplatin in combination with gemcitabine or docetaxel shows no marked differences in efficacy between cisplatin- and carboplatin-containing regimens, although a slight trend favoring carboplatin/gemcitabine treatment may be observed; comparison of toxicity profiles among carboplatin-based regimens suggests advantages for carboplatin/gemcitabine treatment.

Effects of ZD1839 (Iressa, gefitinib) treatment on symptoms and quality of life in patients with advanced non-small cell lung cancer.

Patients with advanced non-small cell lung cancer (NSCLC) who fail to respond to cytotoxic chemotherapy or who cannot tolerate chemotherapy have limited treatment options. In addition, patients with advanced NSCLC often experience disease-related symptoms that impact their quality of life. Treatment goals in this setting include palliation of symptoms and improvement in quality of life, in addition to tumor response or disease stabilization and increased survival.

Epidermal growth factor receptor-targeted therapy with ZD1839: symptom improvement in non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) is a common and frequently incurable disease. Patients with advanced Stage IIIB and Stage IV disease, although not candidates for curative resection, can benefit from receiving treatment (chemotherapy and radiation therapy) that prolongs survival, alleviates symptoms, and/or reduces complications. However, these therapies are often associated with significant adverse events.

Gemcitabine and taxane combinations in non small-cell lung cancer.

Gemcitabine, docetaxel, and paclitaxel are among the most active agents available for the treatment of non small-cell lung cancer (NSCLC). Each has been shown to produce objective responses in approximately 20%-25% of previously untreated patients with advanced or metastatic NSCLC and to improve survival and quality of life when compared to best supportive care. In randomized clinical trials, these drugs have produced response rates and survival outcomes equal to older platinum-based regimens and, when combined with a platinum compound, have produced the best results achieved to date in this disease.

Gemcitabine-based doublets for advanced non-small-cell lung cancer: beyond gemcitabine/cisplatin.

Gemcitabine is one of the most active agents in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). Recent evidence indicates that gemcitabine/cisplatin is among the most active doublets in advanced NSCLC, but the problem of what to give patients who cannot tolerate cisplatin still remains. The combination of gemcitabine/carboplatin is under investigation.

Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation.

These consensus guidelines have been compiled with input from the Scientific Advisors of the International Myeloma Foundation. Their production involved several steps including: A 3-day Scientific Advisors meeting, during which each specific area was presented and discussed (May 2002). Review of key literature, especially randomized study results, but also Medline, Internet, Cochrane database searches, and prior guidelines (Br J Haematol 115: 522-540, 2001).

Biologically targeted treatment of non-small-cell lung cancer: focus on epidermal growth factor receptor.

The epidermal growth factor receptor (EGFR) has emerged in recent years as a key target of molecular therapy for solid tumors. The postembryonic role of EGFR is normally limited. In cancer, however, abnormal EGFR-tyrosine kinase (TK) activity plays a central role in many of the processes involved in tumor progression, such as proliferation, angiogenesis, invasiveness, decreased apoptosis, and loss of differentiation.

Irinotecan, cisplatin/carboplatin, and COX-2 inhibition in small-cell lung cancer.

Recent findings indicate significant prolongation of survival and time to disease progression with irinotecan (CPT-11, Camptosar)/cisplatin vs etoposide/cisplatin in extensive-stage small-cell lung cancer, and a larger-scale phase III trial has been planned to provide more definitive data on the benefits of the irinotecan/cisplatin combination in this setting. Early-phase studies indicate that the activity of carboplatin (Paraplatin) in small-cell lung cancer is comparable to that of cisplatin, and that combining irinotecan on a day 1 and 8 schedule with split-dose carboplatin is feasible. Inhibition of the cyclooxygenase-2 (COX-2) enzyme, which is active in tumorigenesis, may augment efficacy and reduce toxicity of platinum/irinotecan combinations.

Low-dose thalidomide in myeloma: efficacy and biologic significance.

The efficacy of thalidomide at doses as low as 50 mg every other day was first reported at the VII International Multiple Myeloma Workshop in Stockholm, Sweden, in September 1999. This article discusses the duration of responses with low-dose thalidomide and the subsequent efficacy with thalidomide combination approaches. The median effective dose of thalidomide was 200 mg/d.

Whole-body (18)F-FDG PET identifies high-risk myeloma.

Unlabelled: The purpose of this study was to evaluate the clinical utility of whole-body PET with (18)F-FDG in patients with multiple myeloma and related monoclonal diseases.

Methods: Between July 1, 1996, and July 2000, 98 (18)F-FDG PET scans were obtained for 66 patients, with 25 patients having 2 or more scans. The results were compared with routine clinical and staging information, including CT and MRI scans, as indicated.

ZD1839 (Iressa): what's in it for the patient?

Although cytotoxic chemotherapy has had a significant impact on the treatment of some malignancies, its impact against most solid tumors is limited. This is especially true in the case of non-small cell lung cancer (NSCLC) in which about 90% of patients ultimately die from metastatic disease. Although chemotherapy has produced modest improvements in response rates and survival in a subset of patients with advanced NSCLC, its primary objective remains to provide palliation of disabling disease-related symptoms.

The epidemiology of multiple myeloma.

Increases in the incidence of multiple myeloma during this past century implicate environmental factors as important causal agents. The molecular and cytogenetic alterations in multiple myeloma are under investigation, but the precise causes of these abnormalities are largely unknown. Exposure to chemical substances and ionizing radiation are associated with an increased risk of multiple myeloma.

Gemcitabine and nonplatinum combinations in non-small-cell lung cancer.

Gemcitabine (Gemzar), paclitaxel (Taxol), docetaxel (Taxotere), and vinorelbine (Navelbine) are among the most active agents for the treatment of non-small-cell lung cancer and are generally more active than platinum compounds. When combined with a platinum compound, these agents have produced the best survival outcomes seen to date in non-small-cell lung cancer. More than 100 clinical trials have defined and expanded the role of gemcitabine, which has been combined with each of these agents to create novel combinations.

RT-PCR amplicons in the plasma of multiple myeloma patients--clinical relevance and molecular pathology.

The occurrence of RNA (RT-PCR amplicons) in the plasma of 70 patients was quantified: 65 patients with multiple myeloma (MM), 3 with Waldenstrom's macroglobulinemia (WM), 2 with monoclonal gammopathy of undetermined significance (MGUS), and 50 from healthy controls. A 713nt amplicon occurred in 16/18 MM patients in relapse, 5/8 untreated patients, 2,3 WM patients and 1,2 MGUS plasmas. None of the initial specimens from 37 patients in remission nor the 50 healthy controls was positive.

Adjuvant and neoadjuvant chemotherapy for invasive bladder cancer.

Despite technical advances in the surgical or radiotherapeutic treatment of localized invasive bladder cancer, at least 50% of patients ultimately succumb from the growth and progression of microscopic disease beyond the reach of these local treatment modalities. Systemic chemotherapy prior to or immediately following surgery or radiotherapy or concurrently with radiotherapy has been explored in numerous uncontrolled phase II trials and in several randomized phase III trials in an attempt to eradicate this micrometastatic disease burden. Many of these studies have significant flaws in design, implementation, and analysis.

Phase I/II trial of irinotecan, carboplatin, and paclitaxel in advanced or metastatic NSCLC.

This multicenter study enrolled 73 patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). The study design was based on the hypothesis that the non-overlapping toxicities of a 3-drug combination of irinotecan (Camptosar, CPT-11), carboplatin (Paraplatin), and paclitaxel (Taxol) would allow them to be dosed at recommended or standard doses, respectively. Of the 32 patients in phase I portion of the trial, six received irinotecan 40 mg/m2 plus carboplatin at an area-under-curve (AUC) of 6 and paclitaxel 225 mg/m2 on an every-3-week schedule (regimen A).

Identifying and Treating Depression in Women With Cancer: A Primary Care Approach.

In general, depressive disorders in the US are more common in women than in men. In women with cancer, approximately 20% to 25% experience clinically significant depression and/or anxiety at some point during the course of medical treatment. This report profiles the differential diagnosis of depressive disorders as well as special medical variables, treatment options, and follow-up considerations for women with cancer.

Experience with new chemotherapeutic agents in non-small cell lung cancer.

Lung cancer, which is the leading cause of cancer mortality, remains a significant health-care problem among men and women in the United States, despite an overall 20-year decline in the incidence of cigarette smoking. Non-small cell lung cancer (NSCLC) comprises 75 to 80% of all lung cancer cases. The metastatic nature of this disease has been responsible for the poor survival statistics reported to date and emphasizes the need for effective systemic treatment.

The behavioral-cognitive model of pain.

In the elderly patient, for whom pain can be quite complex and multidimensional, a careful assessment of sensory and psychosocial contributions to the pain experience is important. This analysis will allow for the selection of a comprehensive pain regimen that includes behavioral-cognitive techniques. When carefully chosen, and presented in a manner consistent with the patient's cognitive capabilities, psychological techniques afford the elderly patient enhanced self-esteem and self-control without the addition of potentially harmful side-effects.

Criteria for the evaluation of treatment planning systems.

Radiation treatment planning systems (RTPS) are evolving on a rapid and continual basis. After the evaluation of several commercial systems, we have developed a list of features we consider desirable in a product. The goal in the compilation of these criteria was a comprehensive worksheet which categorized the characteristics of RTPS into hardware (computer and peripheral devices), 2-D planning tools, 3-D planning tools, irregular field planning tools, and brachytherapy planning.

High grade soft tissue sarcoma of the flexor fossae. Size rather than compartmental status determine prognosis.

Background: High grade soft tissue sarcoma arising in the popliteal space, axilla, and antecubital fossae (flexor fossae tumors) have by convention been classified as extracompartmental tumors by the accepted staging and grading criteria of the Musculoskeletal Tumor Society (MSTS). Advances in neoadjuvant chemotherapy and radiation therapy have made surgical resection more feasible. The hypothesis to be tested is that compartmental status may not be of prognostic significance if the tumor is adjusted for size, histologic grade, and distant metastasis after undergoing adjuvant chemotherapy and radiation.

The role of thoracic surgery in the management of metastatic osteogenic sarcoma.

Fifty percent of patients with osteogenic sarcoma who develop pulmonary metastases are salvageable with continued effective chemotherapy and thoracotomies, as long as good local control is achieved in the primary tumor. In patients presenting with simultaneous primary tumor and pulmonary metastatic disease, the cure rate is potentially as high as it is in those patients who present with primary tumor alone. However, in the latter patients, curative surgery must be done to obtain permanent local control for the primary tumor, and thoracotomy must be performed to remove residual disease to ensure against recurrent disease.

Thoracotomy in the management of metastatic soft-tissue sarcomas in adults.

The multidisciplinary management of metastatic soft-tissue sarcomas in adults is capable of salvaging approximately half of the afflicted patients. This management includes preoperative chemotherapy for three months, thoracic surgery, continued chemotherapy, and the use of intrapleural mitoxantrone for once-present malignant pleural effusions or suspected pleural seeding of tumor. Thus, there is a definite role for the inclusion of thoracic surgery in the management of patients with soft-tissue sarcomas in whom pulmonary metastases develop.