Biomedical subjects

John J Crowley

Publications and source records attributed to John J Crowley.

18 recordsLinked to original sources

PubMed2005

Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Prostate cancer continues to be a major health threat, especially among African American men. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), which opened on July 25, 2001, was planned to study possible agents for the prevention of prostate cancer in a population of 32,400 men in the United States, including Puerto Rico, and Canada. SELECT is a phase III randomized, placebo-controlled trial of selenium (200 microg/day from L-selenomethionine) and/or vitamin E (400 IU/day of all rac alpha-tocopheryl acetate) supplementation for a minimum of 7 years (maximum of 12 years) in non-African American men at least 55 years of age and African American men at least 50 years of age. SELECT is a large, simple trial that conforms as closely as possible with community standards of care. This commentary discusses the design problems the SELECT investigators had to resolve in developing the trial, including the role of prostate cancer screening, the best forms and doses of the study agents, and estimation of the event (prostate cancer) rate of men on the placebo arm.

Black or African American↗

PubMed2004

Phase I study of tirapazamine plus cisplatin/etoposide and concurrent thoracic radiotherapy in limited-stage small cell lung cancer (S0004): a Southwest Oncology Group study.

PURPOSE: To determine the feasibility and a recommended phase II dose of tirapazamine when combined with chemoradiotherapy in limited-stage small cell lung cancer (LSCLC). EXPERIMENTAL DESIGN: Concurrent chemoradiotherapy consisted of two cycles of cisplatin, etoposide, and once-daily radiation to 61 Gy. Tirapazamine (260 mg/m2) was given 1 h before cisplatin with planned dose escalation to 330 mg/m2 in the absence of dose-limiting toxicity, defined as > or =33% esophagitis (grade 3 or above). Consolidation therapy consisted of two cycles of tirapazamine (330 mg/m2), cisplatin, and etoposide. Complete responders received prophylactic cranial irradiation. RESULTS: Thirty patients were enrolled at the 260 mg/m2 tirapazamine dose. All had performance status of 0-1. By comparison with S9713, a predecessor Southwest Oncology Group study in LSCLC that used the same concurrent chemoradiotherapy without tirapazamine, the present trial showed a higher rate of grade 3-4 esophagitis (34% versus 22%), vomiting (34% versus 23%), and febrile neutropenia (7% versus 2%). The consolidation phase was relatively well tolerated, with grade 4 neutropenia in 44% and febrile neutropenia in 5% of patients. There were two treatment-related deaths: one from neutropenic fever and one from respiratory infection. The overall response rate was 80%, and the median survival was 22 months. CONCLUSIONS: Protocol-defined dose-limiting toxicity was observed at the initial tirapazamine dose, precluding dose escalation. Compared with S9713, the addition of tirapazamine increased the incidence of vomiting, neutropenia, and febrile neutropenia, although the overall toxicity profile remained acceptable. In view of the observed favorable survival, further study of tirapazamine in LSCLC is warranted.

Adult↗

PubMed2004

Clinical efficacy of high-dose dexamethasone with maintenance dexamethasone/alpha interferon in patients with primary systemic amyloidosis: results of United States Intergroup Trial Southwest Oncology Group (SWOG) S9628.

Current therapy of primary systemic (AL) amyloidosis with oral melphalan and prednisone remains unsatisfactory, with a median survival of only 13 months. Between 1996 and 2003, 93 patients with biopsy-proven AL amyloidosis were enrolled in a prospective US national cooperative group trial. Treatment schema consisted of induction therapy with pulse dexamethasone (DEX), followed by maintenance therapy with DEX and alpha interferon. Hematologic complete remissions were observed in 24% and improvement in AL amyloidosis-related organ dysfunction occurred in 45% of patients evaluable for response. Median survival of the entire cohort is 31 months, with an estimated 2-year overall survival (OS) and event-free survival (EFS) of 60% and 52%, respectively. Presence of congestive heart failure and increased level of serum beta2 microglobulin (>/= 0.0035 g/L [3.5 mg/L]) were dominant predictors of adverse outcome. Estimated 2-year OS in patients who are eligible to receive transplants with this approach was 78%. These data demonstrate for the first time in the context of a US multicenter prospective clinical trial that front-line therapy with a DEX-based regimen in AL amyloidosis can lead to durable reversal of AL amyloidosis-related organ dysfunction and prolonged survival.

Aged↗

PubMed2004

Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter.

BACKGROUND: The optimal upper limit of the normal range for prostate-specific antigen (PSA) is unknown. We investigated the prevalence of prostate cancer among men in the Prostate Cancer Prevention Trial who had a PSA level of 4.0 ng per milliliter or less. METHODS: Of 18,882 men enrolled in the prevention trial, 9459 were randomly assigned to receive placebo and had an annual measurement of PSA and a digital rectal examination. Among these 9459 men, 2950 men never had a PSA level of more than 4.0 ng per milliliter or an abnormal digital rectal examination, had a final PSA determination, and underwent a prostate biopsy after being in the study for seven years. RESULTS: Among the 2950 men (age range, 62 to 91 years), prostate cancer was diagnosed in 449 (15.2 percent); 67 of these 449 cancers (14.9 percent) had a Gleason score of 7 or higher. The prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per milliliter, 10.1 percent among those with values of 0.6 to 1.0 ng per milliliter, 17.0 percent among those with values of 1.1 to 2.0 ng per milliliter, 23.9 percent among those with values of 2.1 to 3.0 ng per milliliter, and 26.9 percent among those with values of 3.1 to 4.0 ng per milliliter. The prevalence of high-grade cancers increased from 12.5 percent of cancers associated with a PSA level of 0.5 ng per milliliter or less to 25.0 percent of cancers associated with a PSA level of 3.1 to 4.0 ng per milliliter. CONCLUSIONS: Biopsy-detected prostate cancer, including high-grade cancers, is not rare among men with PSA levels of 4.0 ng per milliliter or less--levels generally thought to be in the normal range.

Aged↗

PubMed2004

Implementation of the Prostate Cancer Prevention Trial (PCPT).

The Prostate Cancer Prevention Trial is a randomized double blind chemoprevention trial of 18,882 men. It is designed to test the difference in the histologically proven prostate cancer prevalence between a group of participants given finasteride and another given placebo for 7 years. We present an overview of the study design, details of the administrative structure of the study and a description of the successful implementation of the accrual phase.

Chemoprevention↗

PubMed2004

Statistical design issues and other practical considerations for conducting phase III prostate cancer prevention trials.

PURPOSE: We briefly describe the purpose of phase II studies as a source of preliminary data for phase III prevention trials, and address statistical and other practical considerations for phase III prostate cancer prevention trials. MATERIALS AND METHODS: Objectives of 2 types of phase II studies and general criteria for validating surrogate end points are described, and statistical considerations needed for planning a phase III prevention trial are explained, including selection of an appropriate study population and end point, the corresponding expected event rate, estimates of loss to followup, and death and compliance rates. If a preventive agent has an impact on the ability to detect prostate cancer, additional study design considerations are then made. Other practical issues are addressed, including collection of biological materials for correlative studies, assessment of quality of life measures and the addition of ancillary studies that may include the collection of additional end points unrelated to prostate cancer. RESULTS: The Southwest Oncology Group is coordinating 2 recently reported phase III prostate cancer prevention trials. The Prostate Cancer Prevention Trial final results of 18,882 men randomized to either finasteride or placebo, and the Selenium and Vitamin E Cancer Prevention Trial has accrued more than half of its goal of 32,400 men. These studies are used to illustrate some statistical design features. CONCLUSIONS: The aforementioned trials provide valuable lessons in the successful design and conduct of phase III prostate cancer prevention trials.

Anticarcinogenic Agents↗

PubMed2004

Mutant DNA in plasma of lung cancer patients: potential for monitoring response to therapy.

The hypothesis tested was that mutant tumor DNA shed into plasma would show predictive value for monitoring response to therapy in non-small cell lung carcinoma patients. Pretreatment plasma specimens from 25 patients on a phase I trial were evaluated, 12 with paired posttreatment specimens, and 138 patients on the Southwest Oncology Group S0003 trial, 38 with paired posttreatment specimens, for the presence of K-RAS mutations. Thirteen tumor specimens from the phase I trial patients and seven tumor specimens from S0003 patients were also available for comparative analysis of K-RAS mutations in tumor tissue and plasma. All patients were treated similarly with paclitaxel, and carboplatin chemotherapy. DNA was extracted and mutational analyses performed using an RFLP-PCR assay. K-RAS mutations were found in plasma DNA in 5/25 of the phase I patients (20%). Median survival was 10 months in all patients, 11.4 months in the wild-type K-RAS group, and 3.3 months in the mutant K-RAS group (P = 0.056). Point mutations in plasma DNA were identical to mutations found in the tumors, confirming the tumor as the source. In two patients with K-RAS mutations pretreatment, posttreatment plasmas were evaluated: a patient with clinical progressive disease retained the mutant DNA, while in a patient with a complete response (CR), the K-RAS mutation was no longer detectable. In an ongoing analysis of S0003 patients, to date, K-RAS mutations have been found in the plasma of 14 patients (10.1%). In 42 matched pre- and posttreatment specimens from both phase I and S0003 trials, four patients had K-RAS mutations pretreatment that were not detectable posttreatment. Of these, two had a clinical CR or partial response, and the other two had stable disease. It was concluded that detection of tumor DNA in plasma is feasible using molecular techniques and that this approach shows promise for monitoring patient response to therapy.

Antineoplastic Agents↗

PubMed2003

Estimating the impact of new clinical trial proven cancer therapy and cancer chemoprevention on population mortality: the Karnofsky Memorial lecture.

PURPOSE: The 31-year "war on cancer" has focused largely on therapeutic (as opposed to preventative) cancer research, which, in both the public and private sector, has received the majority of funding. Meanwhile the prevention of cancer has received less attention. PATIENTS AND METHODS: We analyzed eight positive phase III therapeutic trials of the Southwest Oncology Group, and estimated how the observed improvements in survival from the new therapies would impact mortality at the population level (utilizing Surveillance, Epidemiology, and End Results-data). We compared these results with the impact of the Prostate Cancer Prevention Trial. The measure of impact was person-years saved in the first 5 years. RESULTS: Estimates of person-years saved in the first 5 years included 28,534 from improved treatment of localized bladder cancer and 26,241 from improved treatment of advanced lung cancer, representing, respectively, 31.4% and 2.8% of the person-years which could have been saved for these diseases (the "relative impact of new treatment on survival"). The new therapies from all eight positive phase III trials would have saved 114,641 person-years over the first 5 years. The estimate from the Prostate Cancer Prevention Trial was 99,441 person-years over the first 5 years. CONCLUSION: New cancer therapies have a proven and quantifiable impact on population mortality. Successful cancer prevention has a similarly large impact. However, federal funding for cancer prevention is less than half that of cancer treatment. As a result of its enormous potential for extending life, cancer prevention warrants increased funding and support from federal funding agencies.

Antineoplastic Agents↗

PubMed2003

The influence of finasteride on the development of prostate cancer.

BACKGROUND: Androgens are involved in the development of prostate cancer. Finasteride, an inhibitor of 5alpha-reductase, inhibits the conversion of testosterone to dihydrotestosterone, the primary androgen in the prostate, and may reduce the risk of prostate cancer. METHODS: In the Prostate Cancer Prevention Trial, we randomly assigned 18,882 men 55 years of age or older with a normal digital rectal examination and a prostate-specific antigen (PSA) level of 3.0 ng per milliliter or lower to treatment with finasteride (5 mg per day) or placebo for seven years. Prostate biopsy was recommended if the annual PSA level, adjusted for the effect of finasteride, exceeded 4.0 ng per milliliter or if the digital rectal examination was abnormal. It was anticipated that 60 percent of participants would have prostate cancer diagnosed during the study or would undergo biopsy at the end of the study. The primary end point was the prevalence of prostate cancer during the seven years of the study. RESULTS: Prostate cancer was detected in 803 of the 4368 men in the finasteride group who had data for the final analysis (18.4 percent) and 1147 of the 4692 men in the placebo group who had such data (24.4 percent), for a 24.8 percent reduction in prevalence over the seven-year period (95 percent confidence interval, 18.6 to 30.6 percent; P<0.001). Tumors of Gleason grade 7, 8, 9, or 10 were more common in the finasteride group (280 of 757 tumors [37.0 percent], or 6.4 percent of the 4368 men included in the final analysis) than in the placebo group (237 of 1068 tumors [22.2 percent], P<0.001 for the comparison between groups; or 5.1 percent of the 4692 men included in the final analysis, P=0.005 for the comparison between groups). Sexual side effects were more common in finasteride-treated men, whereas urinary symptoms were more common in men receiving placebo. CONCLUSIONS: Finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer.

5-alpha Reductase Inhibitors↗

PubMed2003

A new staging system for multiple myeloma patients based on the Southwest Oncology Group (SWOG) experience.

We aimed to develop and evaluate a staging system for multiple myeloma (MM) based on easily obtained laboratory measures. The Durie-Salmon stage is most commonly used and is an effective system of patient stratification for clinical trial research. However, the criteria are complex and many laboratory parameters are required to properly stage patients. In this analysis, we focused on two common measures with prognostic importance in MM: serum beta2 microglobulin (beta2m) and serum albumin. Pre-study data on 1555 previously untreated MM patients enrolled on four recent South-west Oncology Group (SWOG) phase III trials were used in the analysis. Staging models were developed and validated using regression tree methods for survival outcomes. SWOG stages were defined as: stage 1, beta2m < 2.5 mg/l (14% of patients, median overall survival of 55 months); stage 2, 2.5 </= beta2m < 5.5 (43% of patients, median overall survival of 40 months); stage 3, beta2m >/= 5.5 and albumin >/= 30 g/l (32% of patients, median overall survival of 24 months); and stage 4, beta2m >/= 5.5 and albumin < 30 g/l (11% of patients and median overall survival of 16 months). This staging scheme was also predictive of event-free survival, first-year mortality and long-term (>/= 5 years) event-free survival. We conclude that although the SWOG stage does not represent a new prognostic marker for MM (cytogenetics, FISH), it could provide a simple alternative to the Durie-Salmon stage for patients with previously untreated MM. Additional evaluation in other MM patient populations is needed to confirm results.

Adult↗

PubMed2003

Vascular access.

Vascular access is the cornerstone of medical therapy in the pediatric population and presents unique challenges. The vessels are small, often exceedingly so, and gaining access may require considerable patience and skill. Peripheral IVs are difficult to place in children, both because of lack of patient cooperation and because of the very small size of many veins. In addition, repeated venipuncture has been identified as one of the greatest stresses in hospitalized children. In the recent past, all forms of central venous access were the preserve of surgeons and were placed in the operating room under general anesthesia. In recent years, pediatric interventional radiologists have described placing peripherally inserted central catheters (PICCs), subcutaneous venous access ports, hemodialysis catheters, and a variety of temporary and permanent central lines even in the smallest children. This has been achieved safely, reliably, and, by dispensing with general anesthesia and operating room time in most cases, at considerable cost savings to the entire health care system. In addition, new forms of reliable, stable access such as the PICC line have made possible outpatient treatment of a wide variety of conditions, particularly infectious, which previously necessitated hospital admission. This has resulted not only in considerable cost saving for the health care system but also improved quality of life for the patient and their family. In this section, I review the current state of pediatric vascular access with emphasis on those areas where pediatric differs from adult practice.

Adolescent↗

PubMed2003

Prognostic factors and response to fludarabine therapy in Waldenstrom's macroglobulinemia: an update of a US intergroup trial (SW0G S9003).

We report an update on a prospective observational trial for Waldenstrom's macroglobulinemia (WM) that called for re-registration to treatment with fludarabine (30 mg/m(2)) upon the development of symptomatic or progressive disease. Patients who did not require therapy for more than 1 year (n = 54) could be distinguished from the 118 untreated patients requiring immediate therapy on the basis of hemoglobin, serum beta(2)-microglobulin (beta2m), C-reactive protein (CRP), albumin, and IgM levels, and lower incidence of extramedullary infiltration. Overall response rate (>or= partial response [PR]) to fludarabine was 38%, with 2% complete remissions (CRs). Event-free and overall survivals were significantly longer in the presence of lower levels of serum beta2m in all cohorts. Using time-dependent covariates, neither the occurrence of response (>or= PR) nor the time to response was associated with superior overall or event-free survival. These data support serum beta2m as the dominant prognostic indicator in WM, and show that this factor alone can provide valuable disease risk assessment. Response to therapy using current criteria is not a reliable predictor for survival in this disease.

Antineoplastic Agents↗

PubMed2003

Cholesterol antagonizes ethanol potentiation of human brain BKCa channels reconstituted into phospholipid bilayers.

The activity of large conductance, Ca2+-sensitive K+ (BKCa) channels, known to control neuronal excitability, is increased by ethanol (EtOH) exposure. Moreover, brain cholesterol (CHS) is elevated after chronic exposure to EtOH, suggesting that membrane CHS may play a role in drug tolerance. Here, we use BKCa channels from human brain (hslo subunits), reconstituted into 1-palmitoyl-2-oleoyl phosphatidylethanolamine/1-palmitoyl-2-oleoyl phosphatidylserine (POPS) bilayers, to examine CHS modulation of EtOH sensitivity. Acute exposure to clinically relevant EtOH levels increases channel activity without modifying conductance. In this minimal system, increases in CHS content within the range found in neuronal membranes lead to progressive antagonism of EtOH action. Furthermore, CHS inhibits basal channel activity with an affinity similar to that of CHS blunting of the alcohol effect. Modification of channel gating by either EtOH or CHS is reduced dramatically by removal of POPS from the bilayer, suggesting a common mechanism(s) of action. Indeed, channel dwell-time analysis indicates that CHS and EtOH exert opposite actions on the stability of channel closed states. However, each agent also acts on distinct dwell states not mirrored by the other, which contribute to the opposite effects of CHS and EtOH on channel gating.

Brain↗

PubMed2002

Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019.

PURPOSE: There are no published survival data after chemoradiotherapy (chemoRT) in pathologically documented stage IIIB non-small-cell lung cancer. Studies of radiotherapy (RT) alone or chemotherapy followed by RT yield 5-year survivals less than 10%. The Southwest Oncology Group (SWOG) employed the same concurrent chemoRT induction regimen used in its predecessor trimodality trial to determine the efficacy, safety, and long-term outcome of replacing postinduction surgery with additional chemoRT. PATIENTS AND METHODS: Eligible patients for SWOG-9019 had pathologic documentation of T4N0/1, T4N2, or N3 stage IIIB non-small-cell lung cancer. They had pulmonary function adequate to withstand combined-modality therapy, identical to the requirements of the previous trial with postchemoRT surgery. Induction therapy was two cycles of cisplatin plus etoposide (PE) concurrent with once-daily thoracic RT (45 Gy). In the absence of progressive disease, RT was completed to 61 Gy, with two additional cycles of cisplatin plus etoposide. RESULTS: Fifty eligible patients were accrued with tumor-node (TN) substage confirmed on central review: 18, T4N0/1; 12, T4N2; and 20, N3. Grade 4 neutropenia was the most common toxicity (32%). Grade 3/4 esophagitis occurred in 12% and 8%. Median follow-up was 52 months, and overall median survival was 15 months (10 to 22, 95% confidence interval). Three- and 5-year survivals were 17% and 15% (5-year T4N0/1, 17%; T4N2, 13%; and N3, 15%). CONCLUSION: Feasibility and long-term survival support the application of these results as a standard against which mature outcomes of chemoRT trials with new chemotherapy agents can be compared. These results also justify use of the SWOG-9019 approach as a control arm in ongoing phase III trials.

Adult↗

PubMed2002

Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients.

The role of maintenance therapy in multiple myeloma is controversial. Recent studies have shown an improvement in both progression-free and overall survival for patients receiving maintenance treatment with a combination of interferon and glucocorticoids, compared with interferon alone. The role of glucocorticoids alone as maintenance therapy has not been previously addressed. We compared alternate-day, oral prednisone at 2 different dose levels (10 mg versus 50 mg) for remission maintenance among previously untreated myeloma patients following a response to induction with standard-dose vincristine, doxorubicin, and dexamethasone with prednisone (VAD-P) or VAD-P plus quinine (VAD-P/Q). There were 250 eligible patients registered on Southwest Oncology Group study 9210 and randomized to receive VAD-P or VAD-P/Q. There were 125 patients achieving at least a 25% tumor reduction following induction therapy who were randomized to either physiologic (10 mg) or pharmacologic (50 mg) doses of alternate-day, oral prednisone until disease progression. At the time of study entry, patient characteristics were similar in VAD-P and VAD-P/Q patients and in the 2 arms randomized to maintenance therapy. After a median follow-up of 53 months, there was no difference in either progression-free or overall survival between the 2 induction regimens. However, from the time of maintenance randomization, both progression-free (14 versus 5 months; P =.003) and overall survival (37 versus 26 months; P =.05) were significantly improved in patients receiving 50 mg as compared with 10 mg alternate-day prednisone. There was no difference in treatment-related adverse events between the groups. Thus, 50 mg, oral, alternate-day prednisone is effective maintenance treatment for multiple myeloma patients who achieve a response to induction chemotherapy. (Blood. 2002;99:3163-3168)

Adult↗

PubMed2002

Economic analysis of vinorelbine plus cisplatin versus paclitaxel plus carboplatin for advanced non-small-cell lung cancer.

BACKGROUND: It is increasingly important to have timely information about the economic impact of new cancer therapies in today's cost-conscious environment. Nearly 170 000 people are diagnosed with lung cancer annually in the United States. We performed an economic analysis alongside Southwest Oncology Group Trial S9509 to estimate the cost-effectiveness of cisplatin plus vinorelbine versus carboplatin plus paclitaxel for patients with advanced non-small-cell lung cancer. There were no statistically significant differences in survival or cancer-related quality of life between the treatment arms. METHODS: Use of both protocol and nonprotocol lung cancer-related health care was tracked for 24 months from the initiation of therapy. To determine expenditures, nationally standardized costs were applied to each type of health care service used, and these were summed over time. Lifetime expenditures and 95% confidence intervals (CIs) for each arm of the trial were calculated with the use of a multivariate regression technique that accounts for censoring. Student's t tests were used to compare the difference in costs between the arms. All statistical tests were two-sided. RESULTS: Cancer-related health care costs over the period of observation averaged 40,292 dollars (95% CI = 36,226 dollars to 44,359 dollars) for patients in the cisplatin plus vinorelbine arm versus 48,940 dollars (95% CI = 44,674 dollars to 53,208 dollars) for patients in the carboplatin plus paclitaxel arm (P =.004), with a mean difference of 8648 dollars (95% CI = 2634 dollars to 14,662 dollars). Protocol chemotherapy drugs and medical procedures costs were statistically significantly higher in the paclitaxel arm (P =.0003 and P<.0001, respectively), whereas protocol chemotherapy delivery costs were statistically significantly higher in the vinorelbine arm (P<.0001). There was no difference between the arms in costs for blood products, supportive care medications, nonprotocol-related inpatient or outpatient care, and nonprotocol chemotherapy. CONCLUSIONS: Treatment with carboplatin plus paclitaxel is substantially and statistically significantly more expensive than treatment with cisplatin plus vinorelbine. The majority of the cost difference is due to the additional cost of the protocol chemotherapy (approximately 12,000 dollars). Notable differences in costs of downstream health care were not apparent.

Adult↗

PubMed2002

Biomarker-based methods for determining noncompliance in a prevention trial.

The Prostate Cancer Prevention Trial (PCPT) is a 7-year randomized trial of 18000 men designed to test a daily dose of finasteride (5 mg/d) for the primary prevention of prostate cancer. Compliance is assessed every 6 months by determining the percentage of pills consumed since the previous visit. In addition, levels of 5 alpha-dihydrotestosterone (DHT) are measured at yearly intervals in a random subset of 5% of participants in the trial as part of a substudy to investigate the potential of this biomarker for monitoring compliance. Motivated by this substudy, we outline three biomarker-based rules for monitoring compliance over time in prevention trials. We make comparisons among the rules using receiver operating characteristic curves. We illustrate the methods using the biomarker DHT in the PCPT substudy with pill counts as a gold standard, and in a simulation study under a hypothetical true gold standard. Our results indicate that simple absolute threshold monitoring rules perform just as well as more complicated rules that utilize the entire biomarker history.

Aged↗

PubMed2002

The evaluation of gemcitabine in resistant or relapsing multiple myeloma, phase II: a Southwest Oncology Group study.

Gemcitabine is a cytosine arabinoside (Ara-C) analog with activity in many human tumor systems. We evaluated the drug's activity in resistant or relapsing multiple myeloma. Gemcitabine 1000 mg/m2 was administered as a 30 minute infusion on days 1, 8, and 15 of a 28-day cycle. No dose escalations were permitted and dose reductions were scheduled for hematologic toxicity. Twenty-nine eligible patients were entered into Southwest Oncology Group (SWOG)-9803. One patient received no treatment and 5 patients had inadequate response assessments. The major toxicity was hematologic with grade 3/4 neutropenia in 9 and grade 3/4 thrombocytopenia in 15 patients. No responses were seen. Stable disease was confirmed in sixteen patients (57%). Median survival was eight months. Gemcitabine as utilized in this trial has shown little activity and is not to be strongly considered for future multiple myeloma trials.

Aged↗