Search PubMed⌕ Search

Biomedical subjects

M Ross

Publications and source records attributed to M Ross.

At least 73 records · Page 4Linked to original sources
PubMed1998

Pharmacokinetic interaction between ondansetron and cyclophosphamide during high-dose chemotherapy for breast cancer.

PURPOSE: Both ondansetron and cyclophosphamide are thought to be metabolized by hepatic microsomal processes. The purpose of this study was to evaluate the potential pharmacokinetic interactions between ondansetron and high-dose alkylating agent chemotherapy. METHODS: A total of 54 breast cancer patients receiving high-dose cyclophosphamide, cisplatin and carmustine were treated prospectively in four sequential cohorts. Cohorts I and II received continuous infusions of both ondansetron and prochlorperazine, and cohorts III and IV received a continuous infusion of ondansetron alone at the same doses. All patients received lorazepam every 4 h. A group of 75 matched historical controls had received a continuous infusion of prochlorperazine with lorazepam. Pharmacokinetic monitoring of each drug used in the high-dose chemotherapy regimen was conducted. RESULTS: Median AUCs of cyclophosphamide in patients receiving ondansetron (73.6 mg/ml x min) were lower than those of the control patients (88.3 mg/ml x min, n = 75, P = 0.0004), but the median cisplatin AUC was approximately 10% higher and no difference in the disposition of carmustine was demonstrated. Patients treated with ondansetron displayed a higher frequency of headaches than the controls. The frequency of achieving complete emetic control was greater in the ondansetron + prochlorperazine groups compared to the ondansetron alone groups and was greater in both these groups than in the prochlorperazine alone group on the first day of therapy only. CONCLUSION: Ondansetron altered the systemic exposure to cyclophosphamide when these agents were administered concomitantly. Ondansetron did not substantially improve overall emetic control when used alone but may improve control in combination with prochlorperazine. Future randomized studies are needed to delineate the effect of ondansetron on the disposition of the active cyclophosphamide metabolites so that clinical implications can be addressed.

Antiemetics↗
PubMed1998

The addition of paclitaxel to continuous infusion 5-fluorouracil is an active regimen for metastatic breast cancer.

Metastatic breast cancer is commonly thought to be incurable. Treatment advances have resulted in increased response rates, although such responses are often more palliative than curative. A regimen of continuous infusion 5-fluorouracil (5FU) or continuous infusion 5-fluorouracil with paclitaxel was studied in patients with metastatic breast cancer and measurable disease. The induction therapy preceded high-dose ifosfamide, carboplatin, and melphalan in a phase I-II trial. Eighty-seven patients were enrolled in the trial. Forty-five received continuous infusion 5-fluorouracil as induction and 42 received 5-fluorouracil and paclitaxel. The single-agent, continuous infusion 5-fluorouracil cohort had one complete response (2%) and eight partial responses (18%). The combination continuous infusion 5-fluorouracil and 3-hour paclitaxel regimen produced four complete responses (10%) and 17 partial responses (40%). The combination regimen of continuous infusion 5-fluorouracil with bolus paclitaxel was well tolerated and with a 50% response rate, is an active regimen for women with metastatic breast cancer.

Adult↗
PubMed1998

Modifying the criteria of the American Joint Commission on Cancer staging system in melanoma.

The currently used staging system in melanoma has not been significantly modified since 1988. While this four-stage system effectively stratifies patients into prognostic groups, additional discriminating criteria have been reported that is not presently incorporated in the staging system. The following additions and modifications are suggested based on a review of the recent literature: 1) for stage I and II patients, Clark's level of invasion is only predictive in patients with melanomas less than 1 mm, the best statistical fit for tumor thickness cutoffs are less than 1 mm, 1 to 2 mm, 2 to 4 mm, and greater than 4 mm, and ulceration should be included as part of the staging system; 2) in stage III patients, the presently used criteria of 3 cm in size needs to abandoned and replaced by the number of lymph nodes involved and the number of lymph node basins involved; and 3) local recurrence presenting as local metastases and satellite disease represent a biologic continuum of regional lymphatic dissemination and should both be classified in the stage III prognostic groups. These modifications, if accepted, should provide the ability to better stratify patients for future adjuvant therapy trials.

Humans↗
PubMed1998

Phase II study of neoadjuvant concurrent biochemotherapy in melanoma patients with local-regional metastases.

Our results with concurrent biochemotherapy in patients with stage IV melanoma have been encouraging. Based on these data, we conducted a phase II study to determine the clinical and histological response rate to neoadjuvant concurrent biochemotherapy in patients with local-regional metastases of cutaneous melanoma (stage III). A total of 65 patients with biopsy-proven, measurable and potentially resectable local-regional disease (nodal, satellite/in-transit metastases and/or local recurrence) were treated with cisplatin 20 mg/m2 intravenously (i.v.) on days 1 to 4, vinblastine 1.5 mg/m2 i.v. on days 1 to 4, dacarbazine 800 mg/m2 i.v. on day 1 only, interleukin-2 9 MIU/m2 per day i.v. by 96 h continuous infusion on days 1 to 4, and interferon-alpha 2a 5 MU/m2 subcutaneously on days 1 to 5, repeated every 3 weeks. Patients underwent surgery after two to four courses of biochemotherapy. Those with tumour regression after two preoperative courses received two additional postoperative courses. Of the 64 patients assessable for clinical response, 28 (44%) had a partial response. Of the 62 patients whose response was assessed histologically, four (6.5%) had no evidence of viable tumour in the surgical specimen (pathological complete remission, pCR) and 27 (43.5%) had a partial response, giving an overall response rate of 50%. Tumour burden did not correlate with response, although patients who achieved a pCR had a significantly lower tumour burden (P = 0.02). Our phase II study indicates that neoadjuvant biochemotherapy is an active treatment for melanoma patients with local-regional metastases. However, it is unclear if biochemotherapy is more active than chemotherapy alone; phase III randomized trials are ongoing to answer this question in patients with stage IV disease.

Adolescent↗
PubMed1998

Selective interactions between prostate fibroblast and epithelial cells in co-culture maintain the BPH phenotype.

Paracrine interactions between primary cultured prostate epithelial cells and stromal fibroblasts were investigated in relation to morphology, growth, androgen sensitivity and secretory activities using co-cultures in which the two populations were separated by a microporous membrane. In this new model system, both cell types maintained several aspects of the differentiated phenotype including the capacity to express 5alpha-reductase iso-enzymes and androgen receptors, to respond to androgens and to secrete prostate-specific antigen by the epithelial cells. Morphological studies demonstrated that the cells grown in co-culture exhibited round nuclei, tonofibrils and microvilli in epithelial cells and elongated nuclei, large amounts of Golgi apparatus and cilia in the fibroblasts, all indicative of the differentiated state. The co-culture system highlights the importance of the metabolic co-operation between prostate fibroblast and epithelial cells for preserving the phenotypic characteristics associated with the human prostate in vivo.

Cell Communication↗
PubMed1998

Secondary myelodysplasia and acute leukemia in breast cancer patients after autologous bone marrow transplant.

PURPOSE: To determine the incidence of myelodysplasia (MDS) and/or acute leukemia (AL) in breast cancer patients after high-dose chemotherapy (HDC) with a single conditioning regimen and autologous bone marrow transplant (ABMT), and analyze the cytogenetic abnormalities that arise after HDC. PATIENTS AND METHODS: We retrospectively reviewed the records of 864 breast cancer patients who underwent ABMT at Duke University Medical Center, Durham, NC, from 1985 through 1996 who received the same preparative regimen of cyclophosphamide 1,875 mg/m2 for 3 days, cisplatin 55 mg/m2 for 3 days, and BCNU 600 mg/m2 for 1 day (CPB). Pretransplant cytogenetics were analyzed in all patients and posttransplant cytogenetics were evaluated in four of five patients who developed MDS/AL. RESULTS: Five of 864 patients developed MDS/AL after HDC with CPB and ABMT. The crude cumulative incidence of MDS/AL was 0.58%. The Kaplan-Meier curve shows a 4-year probability of developing MDS/AL of 1.6%. Pretransplant cytogenetics performed on these five patients were all normal. Posttransplant cytogenetics were performed on four of five patients and they were abnormal in all four, although only one patient had the most common cytogenetic abnormality associated with secondary MDS/AL (chromosome 5 and/or 7 abnormality). CONCLUSION: Whereas MDS/AL is a potential complication of HDC with CPB and ABMT, the incidence in this series of patients with breast cancer was relatively low compared with that reported in patients with non-Hodgkin's lymphoma who underwent ABMT. The cytogenetic abnormalities reported in this group of breast cancer patients were not typical of those seen in prior reports of secondary MDS/AL and appear to have occurred after HDC.

Acute Disease↗
PubMed1998

High-dose chemotherapy with autologous hematopoietic progenitor-cell support as part of combined modality therapy in patients with inflammatory breast cancer.

PURPOSE: To evaluate the feasibility of high-dose chemotherapy (HDC) with autologous hematopoietic progenitor-cell support (AHPCS) as part of combined modality therapy (CMT) in patients with inflammatory breast cancer (IBC). PATIENTS AND METHODS: From April 1993 to March 1997, 30 patients with IBC were treated at our program. Twenty-three patients received neoadjuvant chemotherapy (NAC) before HDC; 18 patients also received adjuvant chemotherapy following surgery, but before HDC. All patients received HDC with high-dose cyclophosphamide, cisplatin, and carmustine (BCNU) with AHPCS. Every patient underwent surgery either before (27 patients) or after (three patients) HDC. Patients received radiotherapy after HDC in addition to tamoxifen if their tumors were estrogen receptor-positive. RESULTS: Thirteen patients experienced grade 3 or 4 nonhematologic noninfectious toxicities. In 12 patients (40%), this represented drug-induced lung injury, which in all cases responded to a 10-week course of corticosteroids. The only treatment-related death was secondary to hemolytic-uremic syndrome (HUS). Another patient suffered grade 4 CNS toxicity, which was completely reversible. All patients engrafted promptly. Eight patients relapsed, five of whom had a poor pathologic response to NAC. Relapses were local (five patients), local plus systemic (one), or systemic only (two). Median follow-up time from diagnosis and HDC is 23.5 (range, 7 to 49) and 19 (range, 4 to 44) months, respectively. Twenty-one patients (70%; 95% confidence interval [CI], 51% to 86%) remain alive and free of disease 4 to 44 months after HDC. Median disease-free survival (DFS) and overall survival have not yet been reached. CONCLUSION: HDC as part of CMT is feasible in patients with IBC. The toxicity of this treatment program is significant, but tolerable. Despite the short follow-up duration, the promising DFS observed in this group of patients warrants randomized studies that include a HDC-containing arm in patients with IBC.

Adenocarcinoma↗
PubMed1998

The localisation and expression of 5 alpha-reductase types I and II mRNAs in human hyperplastic prostate and in prostate primary cultures.

The expression and localisation of mRNAs for 5 alpha reductase Type I (5 alpha R-I) and Type II (5 alpha R-II) isoenzymes in human benign prostatic hyperplasia (BPH) were investigated by RT-PCR and by in mini hybridisation (ISH) using digoxigenin labelled riboprobes. In addition, we also examined the isoenzymes mRNA expression in primary BPH cultures of separated stroma/fibroblast and epithelial cells to determine whether primary cultures are appropriate models in which to investigate 5 alpha R activity and regulation. The results demonstrated conclusively the presence of mRNA encoding both isoenzymes in all specimens so far examined. Additionally, the presence of a functional 5 alpha R-I and -II activity in BPH was confirmed by enzyme assays. ISH studies localised the mRNA expression to both the fibroblast/stromal component as well as the epithelial cells of the hyperplastic tissue. In the glandular regions the expression for both isoenzymes was particularly strong in the basal layers of the epithelium whereas mRNA expression in the secretory cells was less pronounced. Expression of 5 alpha R-I and -II mRNAs in fibroblast was on the other hand variable with high expression in some areas and little in others. These findings were supported by our primary culture experiments which demonstrated that both the fibroblast and epithelial cells maintain a capacity to express both isoenzymes in vitro. In the case of the fibroblast, the capacity to express the isoenzymes was maintained following the sequential passaging of the cells up to passage 6, after which the cells no longer expressed either isoenzyme.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1998

Thigh and calf girth following knee injury and surgery.

Girth measures are commonly used to assess muscle atrophy or joint effusion. Little is known, however, regarding girth measurement changes following knee injury and subsequent surgery. Therefore, the purpose of this study was to compare the thigh and calf girth measurements of involved and noninvolved extremities prior to and following knee surgery for subjects with acute and chronic knee injuries. Of the 40 subjects that were studied, 22 subjects were placed in the acute group (less than 6 months from time of injury to presurgery measurement) and 18 subjects were placed in the chronic group (greater than 6 months from time of injury to presurgery measurement). Thigh and calf girth measurements were taken prior to surgery and then prior to the initiation of outpatient rehabilitation following surgery. For the acute and chronic groups, a three-way analysis of variance (ANOVA) with repeated measures on the extremity, muscle, and time factors was used to analyze the data. For each group, the three-way ANOVA revealed a significant two-way interaction between the extremity and time factors. Post hoc analysis revealed significant differences between involved and noninvolved extremities at both the pre- and post-surgery time periods for the acute and chronic groups. While thigh and calf girth measurement differences existed between the involved and noninvolved extremities prior to and after surgery, the bulk of the girth measurement differences existed prior to surgery for both groups. Based upon the results of this study, the assessment and rehabilitation of the thigh and calf following knee injury and surgery are recommended.

Acute Disease↗
PubMed1998

Assessing the accuracy of conflicting autobiographical memories.

We examined criteria that rememberers and neutral audiences use to validate conflicting memories. In Experiment 1, rememberers described an incident that they recalled differently from someone else from their own and the other person's perspective. Rememberers and audiences then evaluated the accuracy of statements in both accounts, explained their accuracy ratings, and appraised the qualities of the memories. In Experiment 2, dyads who possessed conflicting memories of a shared past episode evaluated each other's recollections. In both studies, rememberers rated their own recollections as more accurate than other people's and based their judgments primarily on the internal coherence of the memories. Rememberers used consensus more frequently and sensory detail less often to evaluate other people's memories than their own. Audiences (Experiment 1) reported examining the consistency between the accounts and their own experiences; they also used consensus and normative behavior to a greater extent than rememberers. In both studies, rememberers judged their own accounts to be more detailed and coherent. Their ratings of detail and coherence predicted their ratings of accuracy.

Adult↗
PubMed1998

Enhancement of cell-mediated immunity in melanoma patients immunized with murine anti-idiotypic monoclonal antibodies (MELIMMUNE) that mimic the high molecular weight proteoglycan antigen.

The purpose of this study was to determine whether a combination of two anti-idiotypic antibodies that mimic the high molecular weight proteoglycan antigen found on most melanoma tumors was capable of enhancing cellular immunity in vaccinated high-risk patients with melanoma. Twenty-eight stage I-IV high-risk patients with melanoma were immunized with a mixture of variable concentrations of MELIMMUNE-1 and MELIMMUNE-2, along with the adjuvant SAF-m, using two immunization schedules. Peripheral blood mononuclear cells were collected before the first immunization and 4 weeks after the final immunization and tested for in vitro proliferation to MELIMMUNE-1 and MELIMMUNE-2 and for cytotoxicity against 51Cr-labeled target cell lines. Additionally, supernatants from in vitro proliferation cultures were tested for interleukin 10 and IFN-gamma levels. Significant in vitro proliferation to MELIMMUNE-1 and MELIMMUNE-2 were observed in postimmunization samples but not in prevaccination samples. The mean stimulation index for MELIMMUNE-2 (33.7 +/- 0.6) was significantly higher than that for MELIMMUNE-1 (13.9 +/- 0.3; P < 0.025). Supernatants obtained from 78% of the in vitro stimulated cultures pre- or postvaccination contained significant levels of interleukin 10 (range, 0.43-142 pg/ml), whereas IFN-gamma levels were elevated in 53% of postvaccination samples (range, 3-245 pg/ml) but not prevaccination samples. More importantly, we were able to generate specific CTL responses in 43% of the patients, which correlated with elevated IFN-gamma levels. These results indicate that MELIMMUNE enhances cell-mediated immunity in patients with melanoma.

Antibodies, Anti-Idiotypic↗
PubMed1997

Pathophysiological and clinical aspects of the CO2 pneumoperitoneum (CO2-PP).

Experimental studies demonstrated a severe cardiac load of the CO2 pneumoperitoneum caused by an accelerated after- and a decreased preload. Patients displaying cardiovascular risks are therefore often rejected from laparoscopic surgery. Hence, the pathophysiological changes and the intraoperative risk of the CO2 pneumoperitoneum in high-risk cardiopulmonary patients (NYHA II-III, n = 15) undergoing laparoscopic cholecystectomy are described. The changes in cardiac after- and preload seem to be due to the elevated intraabdominal pressure rather than transperitoneally resorbed CO2 and are reversible by desufflation. In one patient conversion to open operation had to be performed because of a severe drop in cardiac output and right ventricle ejection fraction. Mixed oxygen saturation was predicting intraoperative worsening in this case. The described pathophysiological changes may seem to be well tolerated even in high-risk cardiac patients. Monitoring of hemodynamics should include an arterial catheter line and blood gas analyses. Pharmacologic interventions or pressureless laparoscopic procedures might not be necessary as long as laparoscopic cholecystectomy is performed.

Aged↗
PubMed1997

A phase I trial of recombinant human interleukin-1 beta (OCT-43) following high-dose chemotherapy and autologous bone marrow transplantation.

We studied the effects of escalating doses of recombinant human IL-1 beta in patients receiving high-dose chemotherapy and ABMT for metastatic breast cancer or malignant melanoma. Sixteen patients received IL-1 beta, 4 to 32 ng/kg/day administered subcutaneously for 7 days beginning 3 h after bone marrow infusion. Three patients at the highest dose level also received G-CSF following completion of IL-1 beta. All patients completed the 7 days of therapy. The majority of patients experienced chills and fever following one or more injections, and seven had severe pain at the injection site. There was one episode of hypotension and one episode of transient confusion at the highest dose level; other significant toxicity was not identified. Recovery of neutrophils to > 0.5 x 10(9)l and platelet transfusion independence occurred at a median of 23 and 22 days, respectively, which was comparable to historical controls. The mean number of bone marrow colony-forming unit granulocyte-macrophage (CFU-GM) per 10(5) mononuclear cells on day +21 post-ABMT was more than twice that of control patients or patients receiving G-CSF or GM-CSF. A linear correlation was found between the dose of IL-1 beta and endogenous concentrations of several cytokines. These patients also displayed significantly higher concentrations of endogenous G-CSF compared to historical controls receiving GM-CSF. While IL-1 beta was moderately toxic and had no effect on recovery of peripheral blood counts after ABMT, the increased number of bone marrow CFU-GM suggests that the addition of G- or GM-CSF to a short course of IL-1 beta may accelerate hematologic recovery.

Adult↗
PubMed1997

High-dose chemotherapy with autologous peripheral blood progenitor cell support for primary breast cancer in patients with 4-9 involved axillary lymph nodes.

Breast cancer patients with more than three involved axillary lymph have a high likelihood of relapse after adjuvant therapy. Early results of administration of high-dose chemotherapy (HDCT) and autologous peripheral blood progenitor cells (PBPC) to patients with primary breast cancer and > or = 10 involved axillary nodes have been encouraging. We performed a multicenter trial to determine whether HDCT could be safely administered to patients with primary breast cancer involving 4-9 axillary lymph nodes. Fifty-four patients with stage II or III breast cancer and 4-9 involved axillary lymph nodes received doxorubicin-based induction chemotherapy, followed by high-dose cyclophosphamide (5.625 g/m2), cisplatin (165 mg/m2), and BCNU (450 mg/m2) and PBPC mobilized by sargramostim (GM-CSF) or filgrastim (G-CSF). After completion of HDCT, patients received radiation therapy to the chest wall or involved breast, plus tamoxifen. Survival and disease-free survival, time to engraftment, and charges associated with HDCT were determined. Plasma concentrations of BCNU were determined and plasma AUC(BCNU) was calculated. Fifty-four patients were evaluable for survival and relapse-free survival. Fifty-two patients received HDCT with PBPC support and were evaluable for toxicity. Fifteen patients (29%) developed late pulmonary drug toxicity, which resolved with a 10-week course of corticosteroids in all but one affected patient, who subsequently died of pulmonary toxicity. Ten patients relapsed a median of 426 days (range 86-1117 days) after the start of induction chemotherapy, seven of whom have died. Forty-three patients are alive and breast cancer-free at a median of 947 days (range 661-1730 days) after the start of therapy, including one patient who developed myelodysplastic syndrome 809 days after the start of HDCT. Actuarial 4-year survival and disease-free survival from the start of treatment are 84 and 71%, respectively. Mean plasma AUC(BCNU) was 400 (range 82-1255) microgxmin/ml and was not statistically different from that measured in historical controls who received 600 mg/m2 of BCNU. Combined hospital and physician charges for patients treated at the University of Colorado decreased from a mean of $125845 for the first four patients to $77126 for the final seven patients. We conclude that HDCT with autologous PBPC can be administered with acceptable safety to patients with primary breast cancer involving 4-9 axillary lymph nodes. An ongoing, prospective randomized trial is evaluating the efficacy of HDCT for this patient group.

Adult↗
PubMed1997

Differential effect of finasteride on the tissue androgen concentrations in benign prostatic hyperplasia.

OBJECTIVE: The 5 alpha-reductase inhibitor, finasteride, provides a logical medical treatment for benign prostatic hyperplasia (BPH). However, the effects of chronic finasteride treatment on prostatic androgen levels, 5 alpha-reductase activity and tissue prostatic specific antigen (PSA) have not been studied. We have examined prostate tissue androgen concentrations and 5 alpha-reductase activity of the gland in men with BPH treated with the drug for 3 months. DESIGN AND PATIENTS: Twenty-eight patients with clinically diagnosed BPH, awaiting transurethral resection of the prostate, were entered in a double-blind placebo controlled study. Nineteen patients were randomly allocated to treatment with finasteride (5 mg daily) and 9 received placebo for 3 months. MEASUREMENTS: Prostate specimens were collected immediately following surgery and analysed for testosterone, dihydrotestosterone (DHT), androstenedione, 5 alpha-reductase activity and PSA. Blood specimens obtained before the start and immediately following treatment were also tested for steroid hormone concentrations and PSA levels. RESULTS: There was no significant difference in the median levels of intraprostatic testosterone (P = 0.77), DHT (P = 0.46) and androstenedione (P = 0.09) between the finasteride and placebo groups. However, the 5 alpha-reductase activity of the placebo group (237.9 pmol DHT/g tissue/30 min) was approximately 10 times that of the finasteride group (21.5 pmol DHT/g tissue/30 min; P = 0.0008). Although we were unable to detect any differences in the PSA concentrations of the prostate glands, there was a significant difference (P = 0.0002) in the median percentage change of serum PSA concentrations for the two patient groups. Serum DHT levels were also depleted (P = 0.038) whilst serum testosterone was increased (P = 0.054) in the finasteride patients when compared to the placebo group. Furthermore our study demonstrated no correlation between the in vitro 5 alpha-reductase activity of the gland and tissue DHT concentrations. CONCLUSIONS: Whilst finasteride treatment induced a reduction in serum dihydrotestosterone and prostatic specific antigen levels with a concomittant increase in blood testosterone concentrations, the impact of the drug on tissue androgen concentrations varied considerably from one patient to another. The differential effect of the drug on tissue androgen concentrations suggests that in the human prostate there are possibly more than one isoform of 5 alpha-reductase responsible for the accumulation of DHT in the gland.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1997

Recent advances in the care of the patient with malignant melanoma.

OBJECTIVE: The authors review the recent advances in the surgical care, staging, and adjuvant treatment of the patient with melanoma. SUMMARY BACKGROUND DATA: Melanoma care has not changed significantly in the last 20 years, and the controversy of elective lymph node dissections in this disease continues to be discussed. Two advances in the care of the patient with melanoma have occurred in the last 3 years to make this an exciting time for clinicians and to offer more hope for the patients with this disease. The concept of the sentinel lymph node (SLN), defined by Morton as the first node in the lymphatic basin that drains the primary melanoma, has been documented to contain the first site of metastatic disease. This technology can be used to stage nodally the melanoma patient, identifying the subgroup of patients (stage III) who have a 5-year survival rate less than 50%. Members of this group are candidates for effective adjuvant therapies. METHODS: A review of the surgical techniques of melanoma care, including recently reported new studies of elective node dissection (ELND) and SLN biopsy in patients with melanoma was performed. In addition, the Eastern Cooperative Oncology Group (ECOG) 1684 trial, which was the basis for the Food and Drug Administration approval of adjuvant interferon-alpha-2b (IFN-alpha-2b) is discussed. RESULTS: The Intergroup Melanoma Trial has reported a survival benefit for performing ELND in patients with melanoma and tumor thickness between 1 and 2 mm or in patients that are younger than 60 years of age. With six reports in the literature that show there is an order to melanoma nodal metastases and that the SLN histology is reflective of the histology of the remainder of the nodal basin, the more conservative SLN biopsy can be performed to adequately stage nodally the patient with melanoma. Patients with nodal metastases who are rendered free of disease with surgical resection have the most to benefit from adjuvant IF-alpha-2b. If one considers only the lymph node-positive group of patients, the survival benefit associate with adjuvant IFN is significant (p = 0.008). CONCLUSIONS: New standards of care for the melanoma patient have been established. Patients at high risk for recurrence have been shown to experience a survival benefit with adjuvant IFN-alpha-2b. With these data, the argument can be made that all patients with melanoma greater than 1 mm should have a nodal staging procedure. Selective lymphadenectomy with SLN biopsy is the least morbid procedure that can be used to obtain this information. If surgeons do not have the nuclear medicine or pathology support to perform lymphatic mapping, then the guidelines of the Intergroup Melanoma Study should be used to apply ELND in a selective fashion. In this way, patients are identified with micrometastatic disease early in their clinical course and can be offered the survival benefit of adjuvant therapy.

Antineoplastic Agents↗