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Biomedical subjects

R O Dillman

Publications and source records attributed to R O Dillman.

At least 55 records · Page 3Linked to original sources
PubMed1996

Malignant melanoma and pregnancy ten questions.

Eight patient case vignettes are presented to illustrate the possible relationship between melanoma and pregnancy. We pose 10 questions regarding the risk and prognosis and answer them based on information in the medical literature. Key conclusions are that there is no evidence that the risk for melanoma is influenced by pregnancy; there is no evidence that abortion in pregnant women diagnosed with melanoma is therapeutic for the mother or necessary to prevent melanoma in the fetus; although as a group, pregnant women diagnosed with melanoma may have a somewhat worse prognosis compared with nonpregnant controls, this difference disappears when patients are matched for factors including age, location and depth of primary, or stage of disease; and there is still a concern that pregnant women may present with more invasive or advanced disease due to hormonal or growth factor effects or delays in diagnosis because changes are attributed to pregnancy.

Adult↗
PubMed1995

The integration of high-dose chemotherapy and biotherapy: initial 5-year experience with autologous bone marrow transplantation in a comprehensive community cancer center.

Perhaps the best example of the integration of chemotherapy and biotherapy is autologous stem cell rescue following high dose chemotherapy. This analysis was undertaken to determine the outcome for patients treated in an autologous bone marrow transplant program, which was initiated in January 1989, and to illustrate the impact which biological response modifiers have had on the toxicity, survival, and costs associated with this aggressive treatment approach. Patients with metastatic cancer and good performance status were treated according to disease-specific treatment protocols. Peripheral blood stem cells [PBSC] came into use in 1990, hematopoietic colony stimulating factors [CSFs] in 1991. Outcome was monitored prospectively from the inception of the program. Five years after the program's inception, 75 patients had undergone 96 intensive chemotherapy treatments followed by autologous PBSC rescue. This included 35 patients with breast cancer, 15 with lymphoma or Hodgkin's Disease, five ovary, four melanoma, three sarcoma, three lung cancer, three leukemia, three testicular, two myeloma, one non-lung small cell carcinoma, and one medulloblastoma. Twenty-one patients underwent back-to-back cycles of intensive therapy and rescue; 14 of whom had breast cancer. Twelve patients were treated in 1989, 14 in 1990, 18 in 1991, 14 in 1992, and 17 in 1993. While four of the first 12 patients died within 60 days of reinfusion of cells in 1989, no patients have died within this time frame as a direct result of therapy during the subsequent four years. No patients have been lost to follow-up. Median survival was only eight months in 1989, but has not been reached for subsequent years. For all patients, median failure-free survival (FFS) is 17.2 months; 1-year FFS is 57%, 2-year 36%, and 3-year 29%. Median overall survival (OS) is 30.4 months; 1-year OS 66%, 2-year 52%, and 3-year 42%. From 1990-1993, for patients with metastatic breast cancer (21), and recurrent lymphoma (15), FFS and OS are comparable to the best results published from academic teaching hospitals. Twenty-one patients have survived over two years, 18 of whom continue in remission. Patients were hospitalized for an average of 31 days in 1989, 28.9 in 1990, 24.5 in 1991, and only 13.0-14.0 days in 1992-1993. Two patients were treated entirely as outpatients. Average hospital charges for the 96 treatments have been $120,000 with a range of $15,000 to $461,000, and currently average around $100,000.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Interferon alpha-2a and external beam radiotherapy in the initial management of patients with glioma: a pilot study of the National Biotherapy Study Group.

The National Biotherapy Study Group conducted a phase I/II trial of alpha-interferon (IFN) plus radiation therapy (RT) in glioma patients to confirm the feasibility of combining these two modalities. Patients newly diagnosed gliomasreceived external beam RT as 180 cGy in 33 fractions over six to seven weeks, five days a week, and IFN at a dose of 3 MIU SC Monday, Wednesday and Friday of each week. IFN was increased to 5 MIU after two weeks and was given for up to 16 weeks. Patients were monitored for toxicity and failure-free and overall survival. There were 12 men and seven women with an age range of 24-77, and a median age of 64 years. There were 12 glioblastomas and seven advanced astrocytomas. Complete surgical resection was carried out in two patients, nine had a partial resection, and eight had a biopsy only. Two patients in the latter group deteriorated rapidly and received < 2 weeks of RT/IFN. One patient stopped IFN because of a skin rash, another stopped because of concurrent pneumonia, and one patient was noncompliant. RT and IFN were well-tolerated; 14 of the 19 patients completed the eight weeks of IFN/RT. However, only three patients took IFN for the maximum of 16 weeks. The only grade 4 toxicities noted were increases SGOT in three, increases alk phos in two, and severe fatigue in four patients. The median failure-free survival was two months, median survival was 7.5 months, and four patients survived beyond one year. The longest survivor was 29.1 months, and one patient is still alive after 20.7 months. IFN/RT can be safely co-administered in patients with gliomas. A randomized trial would be needed to establish clinical benefit.

Adult↗
PubMed1995

Cancer clinical trials in the community setting: a 20 year retrospective.

During the past two decades clinical cancer research in the United States has grown dramatically and has been significantly enhanced by the participation of community hospitals, practicing oncologists, and the creation of community cancer clinical trials organizations. More than 102,000 patients have been enrolled by these community based groups to important clinical trials which have answered questions that have improved cancer treatment in this country and worldwide (Figure 3, Table 8). Practicing oncologists are now well trained in the practice of clinical research and efforts should be directed to ensure that their participation in clinical research continues to increase. There are many obstacles to performing clinical cancer research, but none is greater than the issue of cost. We are currently facing the daunting prospect that health care reform may dramatically curtail or bias future cancer clinical trials. Consumers, providers, politicians, and the general public must be educated to protect and expand the cancer clinical research structure so that we can continue the pursuit of optimal cancer management.

Clinical Trials as Topic↗
PubMed1995

Pharmacokinetics of 111In-labelled monoclonal antibody ZCE-025 and fragments in tumour-bearing mice.

Radiolabelled anti-tumour antibodies, their fragments and derivatives hold promise for imaging and therapeutics in oncology. A better understanding of the pharmacokinetics of these entities is therefore important for clinical applications and management. In the present study, the in vivo behaviour of 111Indium-labelled monoclonal anti-CEA antibody ZCE-025 and its F(ab')2 and Fab' fragments and a Fab' derivative are compared in the nude mouse-human tumour model. The object of the derivative was to improve the tumour uptake of the fragment yet reduce its high renal uptake while continuing to achieve desirable kinetics in the normal tissues. Uptake of the derivative in the tumour was comparable to that of the intact antibody and exceeded that of the underivatized fragments. Moreover, uptake in non-target tissues was lower with the derivative than with the intact entity. The renal uptake of the derivative was dramatically lower than for the fragments. The modelling data strongly suggest that the derivatives will be advantageous for clinical use compared with the underivatized whole antibodies or their fragments.

Animals↗
PubMed1994

Human anti-mouse antibody response in cancer patients following single low-dose injections of radiolabeled murine monoclonal antibodies.

We examined the human anti-mouse antibody (HAMA) response in 61 cancer patients following a single, diagnostic injection of any one of ten 111In conjugated murine monoclonal antibodies. Between 1 and 22 mg of antibody containing 1-5 mCi 111In was administered. The populations studied included 30 patients with colorectal carcinoma (four different antibodies), 22 with malignant melanoma (four antibodies), and nine with prostate cancer (two antibodies). Forty-one percent of the patients developed HAMA within 14 days. Three patients (5%) developed an IgM response, five patients (8%) developed an IgG response, and 17 patients (28%) developed both IgM and IgG. Only 27% of the patients with colon cancer developed HAMA, compared to 55% of the melanoma patients and 56% of the prostate cancer patients. There were no correlations among injected dose, various clinical parameters, and HAMA response. There were variations in the HAMA response to different monoclonal antibodies, but population samples were too small to infer significance. Most of the HAMA responses had a significant proportion of idiotypic or isotypic specificity. Only 1/6 patients who were HAMA negative after the first infusion developed HAMA following subsequent infusions of the same monoclonal antibody. Our data demonstrate that a significant percent of cancer patients develop HAMA following a single, low-dose injection of a radiolabeled monoclonal antibody for diagnostic purposes. This may have important implications for the future therapeutic use of monoclonal antibodies in such patients.

Animals↗
PubMed1994

The clinical experience with interleukin-2 in cancer therapy.

In May 1992, interleukin-2 (IL-2) was formally approved by the U.S. Food and Drug Administration for use in cancer treatment based on its activity in metastatic renal cell carcinoma. IL-2 alone or in combination with activated lymphocytes or other cytokines has significant anti-tumor activity against renal cell carcinoma and melanoma with response rates of 15-20%, some of which are quite durable. Limited anti-tumor effects have been noted in some patients with colorectal cancer and lymphoma. Too few patients have been studied to establish the level of activity in most other specific tumor types. The mechanism of this anti-tumor effect appears to be entirely mediated by the immunostimulatory effects of IL-2. Toxicities are dose related, but are substantial and similar regardless of the schedule of administration. Randomized trials have failed to establish (1) the superiority of high-dose bolus over continuous infusion IL-2, (2) the superiority of IL-2 plus interferon over IL-2 alone, or (3) the superiority of IL-2 plus LAK cells versus IL-2 alone. Further investigation is needed to determine the optimum dose and schedule from the standpoint of cost:benefit and risk:benefit, and to determine the role of IL-2 in the therapy of other malignant diseases.

Carcinoma, Renal Cell↗
PubMed1994

Monoclonal antibody KS1/4-methotrexate immunoconjugate studies in non-small cell lung carcinoma.

The antigen reactive with murine monoclonal antibody (MAb) KS1/4 is expressed on epithelial malignancies and some normal epithelial tissues. Studies were undertaken to evaluate KS1/4-methotrexate (KS1/4-MTX) immunoconjugate in patients with advanced non-small cell carcinoma of the lung. Eleven patients in two different groups received KS1/4-MTX in two different escalating dose infusion schedules with a maximal tolerated dose of 1,750 mg/M2 and a cumulative dose of MTX of 40 mg/M2. Toxicities were similar in both groups and included fever, anorexia, nausea, vomiting, diarrhea, abdominal pain, guaiac positive stool, and hypoalbuminemia. Two patients had an associated aseptic meningitis. One patient had a 50% decrease in two lung nodules without a change in lymphangitic infiltrates. This patient received a second course of treatment and developed an immune complex-mediated arthritis and serum sickness. Four patients mounted a human antimouse antibody response. Post-treatment tumor biopsies documented binding of MAb KS1/4. These studies document the feasibility and potential usefulness of a MAb directed against tumor-associated antigens with the targeting of chemotherapeutic drugs in patients with non-small cell lung carcinoma.

Aged↗
PubMed1994

Antibodies as cytotoxic therapy.

PURPOSE: This review was conducted to characterize the results of trials of unconjugated monoclonal antibodies in the treatment of cancer. This survey does not cover antibodies conjugated to drugs, isotopes, or toxins. METHODS: An English-language literature search was used to identify reports of trials of unconjugated monoclonal antibodies in patients with cancer. RESULTS: Most trials have been pilot or phase I to II in nature. The most encouraging results have been described for various antibodies directed against lymphoma, and for certain monoclonal antibodies that bind to glycolipid antigens on melanoma, sarcoma, and neuroblastoma. Toxicity has not been a major problem with these reagents, but human antimouse antibodies have limited the potential application of murine reagents. CONCLUSION: At present, there are no unconjugated monoclonal antibodies that have proven therapeutic benefit in hematologic malignancies or solid tumors. The most active areas of current interest relate to antibodies to various growth factor receptors and the testing of humanized antibodies.

Antibodies, Monoclonal↗
PubMed1994

Value of prostate cancer screening in a comprehensive community cancer center.

Early detection of prostate cancer may help decrease cancer deaths from this disease despite the increased incidence of prostate cancer. In 1990 and 1991 we conducted one-day "screens" for prostate cancer. This analysis was undertaken to determine the value of the screening procedures for detecting prostate cancer in the community. A total of 579 men, aged 39-84 years (mean 58 years), were evaluated by digital rectal examination (DRE) by a urologist, serum prostate specific antigen (PSA) determination by monoclonal antibody assay, and completion of a detailed questionnaire. Forty-eight percent had not seen a physician in over 2 years; 17% had a 1st- or 2nd-degree relative with prostate cancer. There was a 25% "suspicious" rate including 76 (13%) men with abnormal DRE only, 48 (8%) with abnormal PSA only, and 21 (4%) with abnormal DRE and PSA. Patients with findings suspicious for cancer were recontacted by telephone at 2-month intervals for 6 months to determine outcome because subsequent diagnostic management was at the discretion of practicing physicians. By 6 months, 84% of patients with abnormal findings had seen a physician as recommended. Of the 76 with abnormal DRE only, 11 were biopsied and only one cancer was found (9%). Of 48 with an elevated PSA only, 19 were biopsied; 11 (58%) had cancer (9/9 positive transrectal ultrasound) and 8 had no cancer at biopsy (5/5 negative transrectal ultrasound). Of 21 with both tests suspicious, 11 were biopsied and 9 had cancer (82%). Thus, by 6 months after each screen there was a 3.5% overall cancer detection rate for the whole population screened, a 67% positive biopsy rate among those with an elevated PSA, a 45% positive biopsy detection rate among those with an abnormal DRE, and a 51% positive biopsy rate among all those biopsied. Eighty percent of the PSA elevations were between 4.1 and 10.0 ng/ml. This screening experience yielded several new diagnoses of prostate cancer, and the use of serum PSA levels and ultrasound-guided biopsy was associated with a high positive biopsy rate for cancer.

Adult↗
PubMed1994

Nonoperative management of non-small cell lung cancer: the current cancer and leukemia group B experience.

The Cancer and Leukemia Group B (CALGB) is studying nonoperative management in two subgroups of patients with advanced non-small cell lung cancer. In patients with regional disease, primarily those with bulky N2 or T4 disease or those with contralateral mediastinal involvement (N3), a phase III trial is under way to explore concurrent carboplatin as intensification of local therapy and additional systemic treatment. This builds on prior CALGB work demonstrating the benefits of induction chemotherapy prior to radiation for selected patients with stage III disease. For patients with still more advanced disease, a trial evaluating efficacy and cost of two supportive care modalities during intensive chemotherapy is about to begin accrual. Following its completion, the CALGB plans to evaluate new chemotherapy combinations based on one or more of the exciting new agents now being tested for the nonoperative management of non-small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Effect of radiologic stage III substage on nonsurgical therapy of non-small cell lung cancer.

BACKGROUND: Patients with Stage III non-small cell lung cancer (NSCLC) whose cases are staged or treated surgically have different prognoses, depending on the substage (IIIa, IIIb). It is not known whether the prognostic differences apply to clinically staged nonsurgical cases. The authors wanted to determine whether radiologic Stage III substages, determined by computerized axial tomography (CT) scans, are prognostically important in these patients with NSCLC: In addition, they wanted to determine whether the observed superior survival of selected patients with Stage III NSCLC receiving chemotherapy in addition to radiation therapy (chemo-RT) (Cancer and Leukemia Group B protocol 8433: N Engl J Med 1990; 323:940-5) was influenced by an imbalance in the radiologic Stage III substage. METHODS: Review of pretreatment chest radiographs and CT scans with determination of TNM status and stage was done by the consensus of three readers, who were unaware of which treatment each patient had received (radiation therapy alone [RT] or chemo-RT). RESULTS: Patient characteristics in the two treatment arms were similar. Fifty-five percent of patients receiving RT had Stage IIIa and 33% Stage IIIb disease; in the chemo-RT treatment arm, 73% had Stage IIIa and 25% Stage IIIb disease (P = 0.11). Seven patients (12%) who received RT and one in the chemo-RT treatment arm (2%) had Stage I-II disease on CT scan. Patients with Stage IIIa disease had superior survival to those with Stage IIIb disease (median, 16.5 versus 10.5 months, respectively; P = 0.0045). Within each substage, survival was superior in the chemo-RT (versus RT) treatment arm (Stage IIIa, 17.2 versus 10.7 months, respectively; P = 0.16; Stage IIIb, 12.0 versus 6.9 months, respectively; P = 0.089). CONCLUSIONS: The survival advantage for selected patients with Stage III NSCLC treated with chemo-RT in this study did not result from a more favorable pretreatment radiologic Stage III substage. An advantage for induction chemotherapy was seen in patients with Stage IIIa and IIIb disease. Future studies in this population should prospectively assess and consider stratification for Stage III substage.

Adipose Tissue↗
PubMed1993

Inpatient continuous-infusion interleukin-2 in 788 patients with cancer. The National Biotherapy Study Group experience.

BACKGROUND: Interleukin-2 (IL-2), used alone or in combination with adoptive cellular therapy, is one of the most promising biologic therapeutic agents for cancer treatment. METHODS: The National Biotherapy Study Group conducted 15 trials of continuous-infusion IL-2 involving 788 patients with cancer, 638 of whom were evaluable for tumor response. The protocols included administration of IL-2 and lymphokine-activated killer (LAK) cells, IL-2 and cyclophosphamide, IL-2 and tumor-infiltrating lymphocytes, IL-2 and alpha-interferon (IFN), IL-2 and tumor necrosis factor, and IL-2 and LAK alternating with combination chemotherapy. RESULTS: Responses were detected in 33 of 188 patients (18%) with melanomas, 13 of 167 (8%) with renal cell carcinomas, and 1 of 76 (1%) with colorectal cancers. The median survival times in patients with melanoma and renal cell cancer were 9.6 and 9.3 months, respectively. The proportion of patients surviving 1 year were 35% and 43%, respectively. There were responses in 8 of 51 patients (16%) with lung cancer, but many of these patients received IL-2 and LAK alternating with platinum-based chemotherapy. Four of 23 patients (17%) responded who had breast cancer and received IL-2 and IFN. The protocols involving IL-2 plus adoptive cellular therapy produced a higher response rate than those not involving activated cells (48 of 312 [15%] versus 24 of 326 [7%], P = 0.003); however, there was no difference in survival. There was a 1.8% mortality rate attributed to the complications of IL-2 itself. CONCLUSIONS: IL-2 produces durable tumor responses in some patients, especially in those with melanoma and renal cell carcinoma. Because the drug's toxicity is significant and the overall response rates are low, patient selection may be the most important factor in the clinical use of continuous-infusion IL-2 therapy.

Adolescent↗