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J Kirkwood

Publications and source records attributed to J Kirkwood.

At least 19 recordsLinked to original sources
PubMed2001

Developing indications for the use of sentinel lymph node biopsy and adjuvant high-dose interferon alfa-2b in melanoma.

OBJECTIVES: To convene a multidisciplinary panel of dermatologists, surgical oncologists, and medical oncologists to formally review available data on the sentinel lymph node (SLN) biopsy procedure and high-dose adjuvant interferon alfa-2b therapy for patients with melanoma and to rate the "appropriateness," "inappropriateness," or "uncertainty" of the procedure and therapy to guide clinical decision making in practice. PARTICIPANTS: The panel comprised 13 specialists (4 dermatologists, 4 oncologists, and 5 surgeons) from geographically diverse areas who practiced in community-based settings (n = 8) and academic institutions (n = 5). Participants were chosen based on recommendations from the relevant specialty organizations. EVIDENCE: A formal literature review was conducted by investigators at Protocare Sciences Inc, Santa Monica, Calif, on the risks and benefits of performing an SLN biopsy in patients with stage I or II melanoma and adjuvant interferon alfa-2b therapy in patients with stage II or III disease. The MEDLINE database was searched from 1966 through July 2000, and supplemental information was obtained from various cancer societies and cancer research groups. Panel participants were queried on additional sources of relevant information. Unpublished, presented data were included in abstract form on 1 recently closed clinical trial. CONSENSUS PROCESS: The RAND/UCLA Appropriateness Method was used to review and rate multiple clinical scenarios for the use of SLN biopsy and interferon alfa-2b therapy. The consensus method did not force agreement. CONCLUSIONS: The panel rated 104 clinical scenarios and concluded that the SLN biopsy procedure was appropriate for primary melanomas deeper than 1.0 mm and for tumors 1 mm or less when histologic ulceration was present and/or classified as Clark level 4 or higher. The SLN biopsy was deemed inappropriate for nonulcerated Clark level 2 or 3 melanomas 0.75 mm or less in depth and uncertain in tumors 0.76 to 1.0 mm deep unless they were ulcerated or Clark level 4 or higher. Interferon alfa-2b therapy was deemed appropriate for patients with regional nodal and/or in-transit metastasis and for node-negative patients with primary melanomas deeper than 4 mm. The panel considered the use of interferon alfa-2b therapy uncertain in patients with ulcerated intermediate primary tumors (2.01-4.0 mm in depth) and inappropriate for node-negative patients with nonulcerated tumors less than 4.0 mm deep. Specialty-specific ratings were conducted as well.

Chemotherapy, Adjuvant↗
PubMed2001

Toxicity and response evaluation of the interferon inducer poly ICLC administered at low dose in advanced renal carcinoma and relapsed or refractory lymphoma: a report of two clinical trials of the Eastern Cooperative Oncology Group.

PURPOSE: Phase II studies were conducted to evaluate the safety and efficacy of the interferon inducer Poly ICLC at low doses in advanced renal cancer and relapsed or refractory lymphoma. PATIENTS AND METHODS: Twenty-nine patients with advanced renal carcinoma and eleven patients with lymphoma were treated with poly ICLC. Patients received 0.25 mg/m2 of poly ICLC intravenously twice weekly three days apart until progression or unacceptable toxicity. RESULTS: There were no objective responses. Six patients with renal carcinoma had stable disease as best response with one patient receiving 62 weeks of therapy. Toxicity included grade 3 anemia in 8 patients and grade 4 anemia in one patient. All patients were anemic prior to entry with a median grade 2 anemia at baseline. Grade 4 neutropenia, thrombocytopenia and injection site pain occurred in one patient each. Grade 3 fever, chills or fatigue occurred in four, three, and three patients respectively. Any grade fever occurred in 10 patients (25.6%) and any grade chills occurred in 9 patients (23.1%). CONCLUSION: Poly ICLC at this dose and schedule is well tolerated in both patient populations and is inactive in renal carcinoma.

Adult↗
PubMed2000

Prognostic factors in metastatic melanoma: a pooled analysis of Eastern Cooperative Oncology Group trials.

PURPOSE: To identify factors that are prognostic for survival in patients with metastatic melanoma treated in eight Eastern Cooperative Oncology Group (ECOG) trials conducted over the past 25 years. METHODS: We identified common, significant patient characteristics collected at baseline on 1,362 eligible patients for inclusion in a pooled analysis. Proportional hazards models were used to examine simultaneously the effects of multiple covariates on survival. RESULTS: Median survival was 6.4 months (95% confidence interval, 6.1 to 6.9 months.) Factors conferring the greatest increased risk of death included number of metastatic sites (relative risk [RR] = 1.12), ECOG performance status of 1 or more (RR = 1.49), or metastatic disease in the gastrointestinal (GI) tract (RR = 1.49), liver (RR = 1.44), pleura (RR = 1.35), or lung (RR = 1.19). Prior immunotherapy (RR = 0.84) and female sex (RR = 0. 87) were associated with prolonged survival. Although only 12% of patients responded to protocol treatment, landmark analysis showed this to be a significant prognostic factor (RR = 0.57). A model based on three recent studies in which baseline values for alkaline phosphatase, lactate dehydrogenase (LDH), and platelets were available identified an increased number of sites of metastasis (RR = 1.30), abnormal LDH (RR = 1.89), abnormal alkaline phosphatase (RR = 1.76), abnormal platelets (RR = 1.63), and GI metastases (RR = 1. 66) as prognostic for poorer survival. Response to treatment, when examined by landmark analysis of studies with laboratory parameters, was associated with decreased risk of death (RR = 0.47). CONCLUSION: This study demonstrates the importance and utility of laboratory parameters as prognostic factors for survival and confirmed the deleterious effects of multiple metastatic sites. Prior immunotherapy and female sex were associated with improved prognosis. Prognostic factors identified in this analysis are consistent with the findings of prior published studies and argue for the adoption of laboratory findings in the staging systems that are used for entry and stratification of clinical trials in the future.

Adolescent↗
PubMed1999

Gene therapy with autologous, interleukin 2-secreting tumor cells in patients with malignant melanoma.

We vaccinated metastatic melanoma patients with irradiated, autologous melanoma cells genetically engineered to secrete interleukin 2 (IL-2) to investigate whether an anti-tumor immune response would be induced. Melanoma cell cultures were established from surgical specimens and were engineered to secrete IL-2 by infection with recombinant retrovirus. Twelve patients were vaccinated subcutaneously one, two, or three times with approximately 10(7) irradiated, autologous, IL-2-secreting tumor cells. Treatment was well tolerated, with local reactions at 11 of 24 injection sites and minor systemic symptoms of fever and headache after 6 injections. One patient developed anti-tumor DTH after the first vaccination and showed an increased response after the second vaccination. Anti-autologous tumor CTLs could be detected prevaccination in the peripheral blood of seven patients and their activity increased after vaccination in four patients. No UICC-defined clinical responses were seen, but three patients had stable disease for 7-15 months, one of whom has not yet progressed (15+ months). Thus, patient vaccination with autologous, genetically engineered tumor cells is feasible and safe. Anti-tumor DTH and CTLs can be induced in some patients with such a vaccine.

Adult↗
PubMed1999

Modulation of long-term synaptic depression in visual cortex by acetylcholine and norepinephrine.

In a slice preparation of rat visual cortex, we discovered that paired-pulse stimulation (PPS) elicits a form of homosynaptic long-term depression (LTD) in the superficial layers when carbachol (CCh) or norepinephrine (NE) is applied concurrently. PPS by itself, or CCh and NE in the absence of synaptic stimulation, produced no lasting change. The LTD induced by PPS in the presence of NE or CCh is of comparable magnitude with that obtained with prolonged low-frequency stimulation (LFS) but requires far fewer stimulation pulses (40 vs 900). The cholinergic facilitation of LTD was blocked by atropine and pirenzepine, suggesting involvement of M1 receptors. The noradrenergic facilitation of LTD was blocked by urapidil and was mimicked by methoxamine, suggesting involvement of alpha1 receptors. beta receptor agonists and antagonists were without effect. Induction of LTD by PPS was inhibited by NMDA receptor blockers (completely in the case of NE; partially in the case of CCh), suggesting that one action of the modulators is to control the gain of NMDA receptor-dependent homosynaptic LTD in visual cortex. We propose that this is a mechanism by which cholinergic and noradrenergic inputs to the neocortex modulate naturally occurring receptive field plasticity.

Acetylcholine↗
PubMed1998

Combined chemoradiotherapy vs. radiotherapy alone for early stage squamous cell carcinoma of the esophagus: a study of the Eastern Cooperative Oncology Group.

Squamous carcinoma of the thoracic esophagus has an extremely poor prognosis. This study, EST-1282, was undertaken by the Eastern Cooperative Oncology Group (ECOG) to determine whether the combined use of 5-fluorouracil (5-FU), mitomycin C, and radiation therapy improved the disease-free survival and overall survival of patients with carcinoma of the esophagus, compared to those who received radiation therapy alone. Two- and 5-year survivals were 12% and 7% in the radiation alone arm and 27% and 9% in the chemoradiation arm. Patients treated with chemoradiation had a longer median survival (14.8 months), compared to patients receiving radiation therapy alone (9.2 months). This difference was statistically significant. The same pattern of survival was noted in almost all subgroups independent of whether surgical resection was performed.

Analysis of Variance↗
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↗
PubMed1997

The adjuvant treatment of malignant melanoma.

Interferon alfa-2b has recently been approved by the FDA as the first effective adjuvant therapy for the treatment of the "high risk for recurrence" melanoma patient. In a landmark study (ECOG 1684), the use of high dose Interferon alfa-2b for one year in melanoma patients with either deep primary melanomas or resected nodal metastases resulted in significant increases in overall survival (p = 0.04) and disease-free survival (p < 0.01) compared to the control, observation arm. If one considers only those patients with nodal metastases (89% of the study population) the survival benefit associated with adjuvant Interferon alfa-2b had a p value of 0.008. This survival benefit is on par with the survival benefit experienced with the adjuvant therapy of either breast or colon cancer. Because of the survival benefit associated with the adjuvant therapy, one could argue that any melanoma patient with a significant risk of nodal metastases (tumor thickness greater than 1.0 mm) should have a nodal staging procedure. Lymphatic mapping and sentinel node biopsy techniques are the least morbid and costly method to obtain this information. By performing nodal staging on patients with melanomas greater than 1.0 mm in thickness, effective adjuvant therapy can be applied in a selective fashion, exposing only those patients who have the most to benefit to the toxicities of the therapy.

Antineoplastic Agents↗
PubMed1996

Phase II trial of prolonged continuous infusion of 5-fluorouracil and interferon-alpha in patients with advanced pancreatic cancer. Eastern Cooperative Oncology Group Protocol 3292.

Evidence suggests that interferon-alpha (IFN-alpha) augments the antineoplastic activity of 5-fluorouracil (5-FU) in human adenocarcinoma cell lines in vitro and may enhance the efficacy of 5-FU in patients with advanced colorectal carcinoma. In addition, 5-FU may be more effective when given as a prolonged, continuous i.v. infusion (PCI). The Eastern Cooperative Oncology Group performed a Phase II trial of PCI 5-FU plus IFN-alpha in patients with advanced pancreatic carcinoma. Twenty-six patients with advanced, surgically incurable adenocarcinoma of the pancreas received PCI 5-FU (250 mg/m2 daily for 28 days) in combination with IFN-alpha (5 x 10(6) IU/m2 s.c. thrice weekly). Treatment cycles were repeated 14 days or longer after completion of the previous cycle. Treatment was interrupted prior to day 28 if intolerable toxicity developed, and the dose of 5-FU was reduced in subsequent cycles. Partial response occurred in two of 24 evaluable patients (8%; 95% confidence interval, 0-19%). The majority of the study group (88%) had liver metastases. Patients whose serum lactate dehydrogenase (LDH) was more than twofold elevated developed 5-FU-related toxicity significantly sooner than patients with smaller elevations in serum LDH (9 vs. 22 days; p = 0.003). A similar trend was observed for patients with a more than twofold elevation in serum glutamic-oxaloacetic transaminase (SGOT; 9 vs. 15 days; p = 0.07). In conclusion, PCI 5-FU plus IFN-alpha has minimal activity in patients with advanced pancreatic carcinoma, and elevated serum LDH and/or SGOT may be useful for predicting greater toxicity from 5-FU-based therapy in patients with liver metastases.

Adenocarcinoma↗
PubMed1996

Malignant melanoma metastatic to the tonsil.

Metastasis to the oral cavity from melanoma arising in distant sites is very rare. The authors present three cases of melanoma metastatic to the palatine tonsil: two were cutaneous melanomas and one arose from the mucous membrane of the hard palate. Fewer than 30 cases of metastatic melanoma to the palatine tonsil have been reported, and none have been from mucosal melanoma originating from another mucosal primary site in the head and neck. From this perspective, one of the cases in this article is unique. The authors present clinical histories of the three cases of melanoma metastatic to the palatine tonsil. Two patients were still alive a substantial time after treatment. The case presentations indicate that careful examination of the head and neck should be part of the routine follow-up examination in all melanoma patients.

Adult↗
PubMed1994

Isolation of a new foamy retrovirus from orangutans.

We have isolated a new foamy virus from blood samples taken from two apparently healthy orangutans (Pongo pygmaeus). The older orangutan has since died with encephalopathy after a brief acute illness, while the younger one, his grandson, remains well. These animals and 12 other orangutans had specific antibodies to foamy virus as measured by immunofluorescence. The new foamy virus and the antisera showed strong and specific neutralization, with only weak cross-reaction with other simian foamy virus strains. Southern blotting with gag and env probes of human foamy virus and PCR amplification showed that the new foamy virus, designated SFV-11, is related to, yet distinct from, previously characterized strains from humans, chimpanzees, and monkeys.

Animals↗
PubMed1993

Sequence analysis of the PrP protein from two species of antelope susceptible to transmissible spongiform encephalopathy.

The sequence of the coding regions of the PrP genes of the Arabian oryx and greater kudu have been determined and compared with the related sheep and bovine PrP gene sequences. The oryx gene sequence was found to be very closely related to that of the sheep, encoding just one amino acid difference. The greater kudu gene sequence was found to be more closely related to the bovine, encoding four amino acid differences. The possible influence that the gene sequences have on the transmission of spongiform encephalopathy to these antelope species is discussed.

Animals↗
PubMed1992

Mastectomy versus breast conservation surgery: mental health effects at long-term follow-up.

Between 1984 and 1989, 129 Stage 1 and Stage 2 breast cancer patients were entered into a behavioral study in Pittsburgh. Approximately 70% of these patients had elected to have breast conservation (lumpectomy) surgery, with the remainder choosing mastectomy. Using the Profile of Mood States, a measure of perceived social support, and Karnofsky ratings of physical functional status, patients were assessed 3 to 5 days following surgery and again 3 and 15 months following surgery. The data were analyzed using a repeated-measures analysis of covariance, adjusting for aggressiveness of chemotherapy. Compared to mastectomy patients, patients who received breast conservation surgery were rated as more functional by observers, but they perceived themselves as having less energy and less emotional support, especially over the first 3 months of the recovery period. Because there is accumulating evidence that emotional support may act as a stress buffer in various populations and may have survival value, these findings may be particularly troublesome. This study shows that breast conservation surgery is not a psychosocial panacea. Patients whose breasts are spared, especially younger patients, have psychological symptoms that appear acutely worse in the short run and, in the end, are similar to those of patients who elect to have mastectomies. Therefore, patients choosing lumpectomies are not necessarily psychosocially better off than those electing to have mastectomies. Additionally, these patients, particularly younger patients, may require greater social support and potential mental health interventions than they seem to be receiving.

Adaptation, Psychological↗
PubMed1991

Phase II trial of fluorouracil and recombinant interferon alfa-2a in patients with advanced colorectal carcinoma: an Eastern Cooperative Oncology Group study.

In a pilot clinical trial, treatment of patients with advanced colorectal carcinoma with the combination of fluorouracil (5FU) and recombinant interferon alfa-2a (IFN) resulted in objective tumor regression in 62% of patients. To confirm these findings in a multiinstitutional setting, a phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG) in 1989. The treatment regimen was identical to that used in the earlier study: 5FU 750 mg/m2/d for 5 days as a continuous infusion followed by weekly outpatient bolus therapy and IFN 9MU subcutaneously beginning day 1 and administered three times per week. Doses were modified for gastrointestinal, hematologic, and neurologic toxicity and for fatigue, similarly to those used in the previous pilot trial. Thirty-eight patients were registered; 36 are evaluable for response (one lost to follow-up and one with nonmeasurable disease). All patients had metastatic or locally recurrent disease beyond the scope of resection; 31 of 38 had liver metastases, and 20 of 38 had two or more sites of involvement. Eight patients had grade 4 toxicities, including sepsis (nonneutropenic) (one), watery diarrhea (two), and granulocytopenia (six). Grade 3 neurologic toxicities were observed in two (5%) patients and included slurred speech and gait disturbance. Objective response was 42% (95% confidence interval [Cl], 27% to 58%), including one clinical complete responder and 14 partial responders. Among the responding patients, the median time to treatment failure was 8 months. Two patients remain on treatment at 10+ and 16+ months: median survival has not been reached. The results of this multiinstitutional trial suggest that the addition of IFN to 5FU enhances the objective response rates achieved in patients with advanced colorectal carcinoma and that the toxicities of this regimen are acceptable.

Adult↗
PubMed1990

Estrogen receptor concentration and social factors as predictors of natural killer cell activity in early-stage breast cancer patients. Confirmation of a model.

Previous work of ours has demonstrated that a significant amount of natural killer (NK) activity variance after surgery in stage I and II breast cancer patients could be accounted for by both the estrogen receptor (ER) status of the tumor and by social factors, namely, perceived social support and seeking social support as a general coping strategy. As considerable evidence has accumulated that social support in both animal and human populations may have survival value, we sought to test the reliability of this regression model, using coping and perceived support factor values obtained at 3 months after surgery to account for concurrent follow-up NK activity in this serially assessed group of patients. It was found that the most significant variable predicting NK activity at follow-up was tumor ER concentration, with higher NK activity associated with ER- status. In addition, seeking social support as a coping strategy, as well as the perceived quality of support, also entered the model to account for a significant amount of NK activity variance (multivariate F = 5.25, p less than 0.001). If, as the literature suggests, NK activity is relevant to breast cancer control, and since ER- tumors have a worse prognosis, we suggest here that perhaps such tumors are resistant to control by NK cells because they lack the ability to attract an accumulation of effector cells to the tumor site, or because blocking factors at the site of the tumor prevent local tumor control at the site of action. The finding related to social support also replicates results from an independent sample of breast cancer patients. This finding, taken together with other evidence that this social variable is associated with longer survival in breast cancer populations, underscores the potential importance of this social support variable. Our findings also suggest one possible immunological variable involved, with potential clinical significance, for this patient population.

Adult↗
PubMed1985

Dermatitis produced by applications of monobenzone in patients with active vitiligo.

Six patients with spreading vitiligo treated with applications of monobenzone developed a vesicular dermatitis. The eruption was restricted exclusively to the pigmented areas of the skin. Patch tests applied to pigmented and depigmented skin produced an inflammatory response only within the pigmented areas. The explanation for this puzzling phenomenon is not known.

Adult↗
PubMed1985

Demographic study of clinically atypical (dysplastic) nevi in patients with melanoma and comparison subjects.

We examined 296 patients with a history of melanoma and 145 controls for the presence of atypical (dysplastic) nevi. We found that 34% of patients with melanoma and 7% of controls had clinically atypical (dysplastic) nevi. Patients and controls with atypical (dysplastic) nevi had more nevi than the subjects without. The number of nevi varies negatively and significantly with age (r = 0.37, P less than 0.001). Ten % of patients and controls had hypopigmented halos around one or more nevi. Both patients and comparison subjects with atypical (dysplastic) nevi tended to have this subtle variant of halo nevi more often than those without (r = 0.17, P less than 0.01). The number of nevi on the irides of melanoma patients was greater than that in the comparison group. The results of this study suggest that patients with a melanoma exhibit more commonly cutaneous and ocular pigmentary lesions than comparison subjects without a melanoma.

Adolescent↗