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Biomedical subjects

W A Robinson

Publications and source records attributed to W A Robinson.

At least 19 recordsLinked to original sources
PubMed1992

Low-dose alpha-interferon treatment of chronic myeloid leukemia.

We treated 29 patients with chronic-phase and accelerated chronic myeloid leukemia (CML) with alpha-interferon in a dose of 2 mU/m2 given subcutaneously daily for 30 days and then three times per week. Most had received prior treatment. Three patients have had sustained hematologic and karyotypic remissions after a median of 22 months of treatment. Three further patients have had complete hematologic and partial karyotypic remissions. At a median follow-up of 48 months, the median survival has not been reached. This dose of alpha-interferon may induce sustained remissions even in pretreated patients and may prolong survival in CML.

Adult↗
PubMed1992

Breast metastases from malignant melanoma.

We review here 15 patients with cutaneous malignant melanomas metastatic to the breast. All but one were premenopausal females with a median age of 38 years. Most patients had a primary lesion on the upper extremities or trunk (80%), with only one patient having a lower extremity primary. The median interval between diagnosis of the primary and breast involvement was 33 months, with one patient developing breast involvement 11 years later, at the time of her second pregnancy. Five patients had bilateral breast involvement, and all had other sites of metastases at the time of diagnosis. The median survival after diagnosis of breast metastases was 10 months, portending a poor prognosis.

Adult↗
PubMed1992

Preferential chromosome 11q and/or 17q aberrations in short-term cultures of metastatic melanoma in resections from human brain.

Thirteen specimens of metastatic malignant melanoma resected from eight patients undergoing craniotomy were analyzed cytogenetically from short-term cultures. All patients had chromosome 1 aberrations, as did three of four patients with metastases only to extracranial sites. Both groups had variable involvement of chromosomes 3, 6, 7, and 8. Only those with brain metastases had 11q and/or 17q involvement in six of eight patients. In reported cases of nonbrain metastases, when chromosome 11 was involved, the short arm was usually deleted or replaced through translocation; on the contrary, in reports on patients with brain metastases, the long arm of chromosome 11 was deleted at q23 or was the recipient of a translocation at q23, and/or 17q was present as an isochromosome. These aberrations were similar to those found in the patients with brain metastases in this report. Two patients undergoing brain resections did not show 11q or 17q aberrations, one near diploid with t(10;19) and the other near hexaploid with few structural rearrangements. The neural cell adhesion molecule gene is located near 11q23, and the neural growth factor receptor is located near 17q21-q22. The relevance of these genes to brain metastases in melanoma is under investigation.

Brain Neoplasms↗
PubMed1992

A case-control study of late recurrence of malignant melanoma.

Late recurrence of malignant melanoma is uncommon but appears to be a growing problem. It is unclear whether late recurrence has a better prognosis than early recurrence. Since the answer may influence treatment, we compared recurrence sites and subsequent survival in 35 patients with disease-free intervals of 72 to 240 months (median: 127 months) with 35 case-controls who had relapse at 4 to 56 months (median: 26.7 months). The distribution of recurrence sites in early relapse was 66% in regional nodes or soft tissue and 34% in distant soft tissue or viscera. In late relapse, this distribution was 49% in regional nodes or soft tissue and 51% in distant soft tissue or viscera (no significant differences). Median survival for patients with early and late recurrences in regional nodes or soft tissue was 26 and 44 months, respectively (no significant differences); 5-year survival was 27% and 33%, respectively (no significant differences). Median survival was similar for early or late relapse in distant soft tissue or viscera (8 and 10 months, respectively), as was 5-year survival (0% and 6%, respectively). These results suggest that the metastatic pattern and survival after recurrence are similar for patients with early and late recurring melanoma.

Case-Control Studies↗
PubMed1991

Role of recombinant alpha-interferon in the treatment of advanced cutaneous malignant melanoma.

A total of 65 patients with advanced cutaneous malignant melanoma (MM) have now been treated with interferon alpha-2b (Intron A) at a dose of 10 million IU/m2 administered subcutaneously thrice weekly. Fifty-one patients were evaluable for response, and 4 of these (7.8%) achieved complete remission; 2 of these 4 remain so at 37 + and 54 + months. Six additional patients achieved a partial remission. All responders had subcutaneous, lymph node and/or pulmonary metastases only. In all responders, therapy was continued for a total of 12 months. The vast majority of patients experienced side effects, largely flu-like symptoms, mild leukopenia and mild hepatocellular dysfunction. No evidence of cumulative toxicity was observed. Our experience indicates that interferon alpha-2b is active in patients with advanced cutaneous MM.

Adult↗
PubMed1991

Phase II trial of piritrexim in metastatic melanoma using intermittent, low-dose administration.

A phase II trial of piritrexim (2,4-diamino-6[2,5-dimethoxybenzyl]-5-methyl pyrido-[2,3d] pyrimidine, 301U74; PTX) was conducted for patients with metastatic malignant melanoma using an intermittent, low-dose oral administration schedule. PTX was administered at a starting dose of 25 mg orally three times per day for 5 days weekly for 3 weeks followed by 1 week of rest. Thirty-one patients were entered onto the study. Among 31 patients assessable for response, there were two complete responses (CRs) and five partial responses (PRs) for a response rate (CR plus PR) of 23% (95% confidence limit, 10% to 42%). Five responses occurred in soft tissue lesions, and two responses occurred in lung lesions. The initial dose schedule was well tolerated. The dose-limiting toxicity was myelosuppression. PTX administered in this schedule appears to be active against malignant melanoma. Further clinical trials to confirm these results are underway.

Administration, Oral↗
PubMed1991

Single-dose murine monoclonal antibody ricin A chain immunotoxin in the treatment of metastatic melanoma: a phase I trial.

To determine the maximally tolerated dose of a ricin A chain-conjugated antimelanoma antibody (XomaZyme-Mel), 20 patients with metastatic melanoma were treated with escalating doses of the murine immunotoxin given as single intravenous infusion over 30 minutes. The starting dose was 0.6 mg/kg and was escalated in five groups to a maximum of 1.6 mg/kg. The maximally tolerated dose was 1.25 mg/kg as three of six patients treated at 1.6 mg/kg developed unacceptable toxicity. The dose-limiting toxicity consisted of profound fatigue, myalgias, and arthralgias. These occurred within 4 days and resolved in 7 to 10 days. Other non-dose-limiting toxicities encountered consisted of hypoalbuminemia, weight gain, peripheral edema, mild hypotension, and flu-like syndrome; the severity of these was also dose related. In addition, two allergic reactions occurred, one severe. There was one durable complete response of 12+ months' duration and one brief mixed response lasting 3 months. We conclude that the maximum tolerated single dose of XomaZyme-Mel is 1.25 mg/kg. Phase I studies evaluating 1.25 mg/kg given in multiple doses at 2- to 4-week intervals and phase II studies to determine the response rate of a single 1.25 mg/kg dose are warranted.

Adult↗
PubMed1990

Surgical treatment of brain metastases in malignant melanoma.

The authors report the results of a retrospective review of 13 patients who underwent 19 craniotomies for resection of metastatic malignant melanoma at the University of Colorado (Denver, CO) between 1983 and 1989. There was preoperative evidence of extracranial disease in 11 patients. Eight patients had more than one intracranial metastasis at operation. Intraoperative ultrasound was used in 18 of the 19 craniotomies to minimize surgical trauma to the brain. The 30-day mortality was zero. The 30-day morbidity was minimal. No patient acquired a new neurologic deficit as a result of surgery. All patients regained at least their preoperative level of functioning. Six of the patients who were living at the time of review have been followed for 4 to 25 months (median, 7.5 months). The seven patients who were dead at the time of review survived 4 to 18 months (median, 10 months). These results compare favorably with the survival of untreated patients with metastatic melanoma to the brain (median, 1 month), patients treated with radiation therapy alone (median, 2-4 months), and those treated with chemotherapy alone (median, 2-4 months). The excision of metastatic melanoma from the brain, although not curative, may increase survival in patients with this problem with little morbidity and mortality even in the presence of other metastases.

Adult↗
PubMed1990

Cigarette smoking, blast crisis, and survival in chronic myeloid leukemia.

We reviewed the records of all patients with chronic myeloid leukemia (CML) seen in the CML Clinic of the University of Colorado Health Sciences Center between 1968 and 1987 for a history of cigarette smoking. Patients who smoked for five or more pack/years within the ten years preceding, or after the diagnosis of CML, were defined as smokers. Adequate smoking histories were obtained on 122 patients. Eighty-seven of these were non-smokers and 35 were smokers by the above criteria. The smoking group had a higher predominance of males, an older median age, and were diagnosed earlier in the course of the 20 year study. Seventy-two patients had died at the time of analysis. All but one, a non-smoker, died from the development of blast crisis. The overall median actuarial survival was significantly reduced for smokers (35 months) as compared to non-smokers (47 months). This was particularly striking for patients who had succumbed to the disease, with a median survival of 30 months in smokers versus 46 months in non-smokers. Although various explanations could explain the differences noted, we conclude that cigarette smoking has an adverse effect on the development of blast crisis and survival in chronic myeloid leukemia.

Adolescent↗
PubMed1990

Malignant melanoma as a model for cancer education and prevention. 1989 Harvey lecture American Association for Cancer Education.

Cutaneous malignant melanoma is one of the most rapidly increasing and highly fatal cancers in the world today. Current estimates suggest that 1 in 90-100 Caucasians will develop MM by the year 2000, and 20%-30% will eventually die of the disease. The cause of the epidemic of malignant melanoma is clearly increasing exposure to the sun from lifestyle and clothing habits that have changed over the past 50 years. The disease occurs primarily in preexisting nevi in sun-exposed sites in specific high risk populations who can be, and have been, defined. These are primarily middle- and upper middle-class Caucasians with blue eyes, brown or blonde hair, and fair skin, with predominantly indoor occupations who spend, or have spent, considerable time outdoors in leisure and other activities. The presence of a clearly definable cause (exposure to the sun) in specific risk groups, the ease of early detection by simple means, and the devastating outcome of late diagnosis make malignant melanoma an ideal model for teaching the basic tenets of cancer causation, development, and prevention to the public and professionals alike.

Adult↗
PubMed1989

Prophylactic penicillin for intraoral wounds.

We conducted a prospective, double-blind, placebo-controlled study in adult patients to determine whether prophylactic penicillin prevents infection in intraoral lacerations secondary to minor trauma or seizures. Uninfected full-thickness, mucosal-only, or through-and-through wounds presenting within 24 hours of injury were considered. Management consisted of cleansing, irrigation, debridement, and closure as indicated: no topical antibiotics were applied. Patients were randomly assigned to receive penicillin VK 500 mg or identically appearing placebo four times daily for five days. Home wound care was standardized and patients were followed for a minimum of four or five days. Infection was assessed clinically. Seventy-six patients were enrolled and 62 completed the study. Penicillin (30) and placebo (32) groups were similar in all parameters except wound etiology; assault was more common in the placebo group (P = .02). Two infections occurred in patients receiving penicillin, and six infections were seen among placebo-treated patients (P = .05, beta = 0.17). When patients poorly compliant with therapy were eliminated from analysis, none of the penicillin-treated patients and five of the placebo-treated patients developed infections (P = .027). Our data suggest that patients with intraoral wounds may benefit from prophylactic penicillin if compliant with their therapy. More studies are needed to further delineate the usefulness of prophylactic antibiotics for these wounds.

Administration, Oral↗
PubMed1989

Intranasal administration of deferoxamine to iron overloaded patients.

We examined the effect of intranasal administration of deferoxamine on iron excretion in seven patients with iron overload secondary to chronic transfusion therapy. Deferoxamine was administered in doses of 0.75 to 3.0 gm given over 12 hours in a variety of dosing schedules. There was a probable, though not significant, dose response relationship between the amount of iron excreted and the dose administered. The amount of iron excreted was 10%-15% of that obtained using the same dosage of deferoxamine given by the subcutaneous route over the same time period. Hourly administration was more effective than less frequent administration. Addition of taurodeoxycholate to deferoxamine did not increase its absorption as measured by the levels of iron excretion. Side effects were few and consisted mainly of mild nasal irritation and a bad taste in the mouth. Nasal administration of deferoxamine may be a useful adjunct to iron chelation in patients receiving chronic transfusion therapy, particularly in those who are noncompliant with parenteral means of administration.

Administration, Intranasal↗
PubMed1989

Sequential use of indium-111 labeled monoclonal antibodies 96.5 and ZME-018 does not increase detection sensitivity for metastatic melanoma.

Two indium-111 labeled anti-melanoma murine monoclonal antibodies (MAb), 96.5 and ZME-018, each recognizing separate antigens on melanoma cells, were administered intravenously to 17 patients with melanoma in a sequential fashion to determine whether: 1) additional tumor sites could be imaged with the combination compared to a single Mab; 2) the first MAb influenced the biodistribution and tumor localization of the second; and 3) significantly toxicity occurred with the combination. Patients were randomized to receive either 96.5, followed by ZME-018, ZME-018 followed by 96.5, or each MAb followed by itself (controls). Infusions of the second MAb occurred 10 days after the first infusion. Gamma camera images were obtained 72 hours after each antibody infusion. There were 139 known metastatic sites of which 72 lesions were localized by either MAb for an overall sensitivity of 52%. The detection rate was higher when lesions only greater than 1.5 cm were considered. Imaging results were independent of MAb administration sequence. When ZME-018 was given as the first infusion, when ZME-018 was given as a second infusion (p = NS). However, mean sensitivities using 96.5 as the first or second infusion were 48% and 66% respectively (p = NS). There was not a significant number of sites detected by MAb 2 that were missed by MAb 1. Human anti-murine antibody (HAMA) response occurred in seven of eight patients studied; two patients who experienced toxicity had levels of HAMA greater than 2000 ng/ml. We conclude that the use of these two murine anti-melanoma monoclonal antibodies given in sequential fashion did not significantly change the imaging sensitivity from that seen with each individual antibody. Moreover, with the exception of one patient, mean plasma half-life of the MAb did not change significantly, suggesting that overall clearance mechanisms were not saturated by the consecutive doses of monoclonal antibody or significantly altered by the presence of HAMA.

Adult↗