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Biomedical subjects

M Markman

Publications and source records attributed to M Markman.

At least 289 records · Page 16Linked to original sources
PubMed1987

Long-term survival of advanced refractory ovarian carcinoma patients with small-volume disease treated with intraperitoneal chemotherapy.

Ninety ovarian carcinoma patients failing primary intravenous (IV) combination chemotherapy were treated with cisplatin-based combination intraperitoneal therapy. Sixty-five patients had residual disease greater than 2 cm at the start of intraperitoneal therapy. Their median survival was 8 months. Twenty-five patients had disease less than 2 cm; their median survival was greater than 49 months, and the survival curve has an apparent plateau at 69%, with no relapses having occurred after 32 months. The median survival for all 90 patients was 15 months. The median duration of follow-up for all patients was 37 months. These results confirm the critical role of tumor bulk in determining the effectiveness of intraperitoneal therapy, and suggest a role for intraperitoneal salvage treatment in patients with small-volume disease.

Actuarial Analysis↗
PubMed1987

The pharmacology of intraperitoneally administered bleomycin.

The clinical pharmacology of intraperitoneally administered bleomycin was examined in 11 patients with malignancies confined predominantly to the peritoneal cavity. Bleomycin (60 mg/m2) was mixed in 2 L of 0.9% NaCl, and administered rapidly into the peritoneal cavity via a Port-a-Cath (Pharmacia Nu Tech, Inc, Walpole, MA). The cavity was drained following either a four- or eight-hour dwell time. Bleomycin concentration in the peritoneal cavity and plasma was determined by radioimmunoassay. A total of 15 courses was studied. The peak peritoneal: plasma concentration ratio averaged 22, and total exposure for the peritoneal cavity averaged seven-fold greater than that for the plasma. The peritoneal and plasma half-lives for bleomycin were 3.2 and 6.0 hours, respectively. The peritoneal clearance of bleomycin averaged 11.3 mL/min/m2. Abdominal pain occurred on 47% of courses; other toxicities included fever, skin rash, and mucositis. We conclude that there is a substantial pharmacologic advantage to the peritoneal route for tumors confined to the peritoneum, but that the advantage is less, and the local toxicity greater, than that found with the intraperitoneal administration of many other anticancer drugs.

Bleomycin↗
PubMed1987

Clinical cancer research, DNR orders, and medical economics: a complex interrelationship.

Despite the dramatic success achieved over the past few years in improving the survival of individuals with cancer, treatment for many patients with advanced malignancies remains far from satisfactory. Unfortunately, centers engaged in clinical cancer research are currently faced with the dilemma of dealing with increasingly complex and expensive experimental treatment regimens at the same time funding for such research and patient care is decreasing. A further complicating factor is the high cost of caring for terminally ill patients in cancer centers, particularly those potentially requiring intensive life support. This paper reviews the problems facing both clinical cancer investigators and hospitals involved with cancer research and proposes several suggestions for dealing with these increasingly complex issues.

Antineoplastic Agents↗
PubMed1987

Intracavitary administration of biological agents.

The intracavitary delivery of biological agents is based on sound pharmacologic, immunologic, and physiologic rationales. Results of early-stage clinical trials have confirmed both an advantage for exposure of the body cavity to the biologicals as compared with that of the systemic circulation following intracavitary drug delivery, as well as the suggestion of definite clinical utility. Trials that are in progress and those planned for the future will hopefully define optimal drug combinations, concentrations, and treatment schedules. Ultimately, randomized controlled trials will be required to define a role for such therapy as compared with standard therapeutic approaches to diseases principally confined to body cavities.

Adjuvants, Immunologic↗
PubMed1987

Supportive care.

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Antiemetics↗
PubMed1987

Current status of intracavitary chemotherapy.

While the most effective treatment regimens and both short-term and long-term toxicities remain to be determined, it is not unreasonable for clinicians treating patients with minimal residual disease following cisplatin-based systemic chemotherapy for ovarian carcinoma to try cisplatin by the intraperitoneal route.

Antineoplastic Agents↗
PubMed1987

Intraperitoneal chemotherapy for ovarian carcinoma.

Investigators at several centers have begun to explore the potential utility of the intraperitoneal administration of chemotherapeutic agents as therapy for advanced ovarian carcinoma. Recent pharmacokinetic modeling studies have suggested and initial clinical trials have confirmed an advantage for cavity exposure to certain drugs compared to systemic exposure when the agents are delivered directly into the peritoneal cavity. While objective responses have been observed in patients with refractory disease, there are both practical and theoretical problems with this approach to the treatment of ovarian carcinoma. Eventually randomized controlled trials will be required to define a role for this innovative therapeutic technique.

Animals↗
PubMed1986

Cisplatin administered by the intracavitary route as treatment for malignant mesothelioma.

Twenty-one patients with malignant mesothelioma were treated with an experimental intracavitary chemotherapy regimen of weekly intraperitoneal or intrapleural cisplatin (90-100 mg/m2) with simultaneous intravenous sodium thiosulfate delivered to protect against cisplatin-induced nephrotoxicity. One of eight patients (12.5%) receiving intrapleural therapy and nine of 13 patients receiving intraperitoneal therapy demonstrated objective evidence of a clinical response, including three surgically defined major tumor regressions (23%). Patients receiving intrapleural treatment had more advanced disease prior to therapy than those receiving intraperitoneal therapy. It was concluded that intraperitoneal cisplatin is an active treatment program for intra-abdominally localized mesothelioma. Additional investigation of intrapleural cisplatin should be undertaken in a patient population with less advanced disease or following surgical debulking.

Actuarial Analysis↗
PubMed1986

Hypomagnesemia following high-dose intracavitary cisplatin with systemically administered sodium thiosulfate.

Seventy-one patients receiving a minimum of two courses of high-dose intracavitary cisplatin (100-200 mg/m2/course) with i.v. thiosulfate administered to protect against cisplatin-induced renal insufficiency were retrospectively evaluated to examine the influence of thiosulfate and large cumulative doses of cisplatin on the incidence of hypomagnesemia. Only 8% of 50 patients who had normal serum magnesium levels prior to the initiation of the experimental program became hypomagnesemic during the therapeutic trial. Similarly, while 67% of the 21 patients with low initial serum magnesium levels remained hypomagnesemic, 33% had normal serum levels at the completion of therapy. It is suggested that the intravenous administration of thiosulfate might have been responsible for the strikingly low incidence of hypomagnesemia in this patient population. A prospective evaluation of the utility of sodium thiosulfate in preventing cisplatin-induced renal magnesium wasting appears indicated.

Adult↗
PubMed1986

Cytotoxic intracavitary chemotherapy.

The intracavitary administration of chemotherapeutic agents for their cytotoxic properties as therapy for tumors confined to body cavities has significant theoretical appeal. Pharmacokinetic evaluation of several clinically useful antineoplastic drugs has confirmed modeling predictions that suggested a major advantage for cavity exposure to the agents compared with that of the plasma when the drugs are delivered directly into the body cavity. As the direct penetration of the agents into tissue is quite limited, the greatest potential utility of this therapeutic approach would be in patients with microscopic residual disease following debulking surgery or as therapy for patients with a high risk of intraperitoneal recurrence. Major toxicities of this innovative technique include abdominal pain (chemical serositis) and infection. Additional clinical evaluation will be required to define a role for cytotoxic intracavitary chemotherapy in the management of malignant disease.

Animals↗
PubMed1986

Vancomycin-induced vasculitis.

A patient receiving vancomycin for a serious staphylococcal infection had a lupus-like syndrome characterized by a malar rash, pain and erythema of the cartilage of both ears, and tender erythematous and hemorrhagic lesions of the finger tips. Biopsy and direct immunofluorescence study of the skin showed changes consistent with the diagnosis of lupus erythematosus. The possible development of a drug-induced vasculitis or lupus-like syndrome should be added to the list of rare toxic effects of vancomycin.

Drug Eruptions↗
PubMed1986

Ip chemotherapy employing a regimen of cisplatin, cytarabine, and bleomycin.

Thirty-seven patients with refractory ovarian carcinoma or other malignancies principally confined to the peritoneal cavity were treated with a combination ip chemotherapy regimen consisting of cisplatin (100 or 200 mg/m2), cytarabine (1,200 mg/m2), and bleomycin (15 or 2 U/m2) repeated at 28-day intervals. Sodium thiosulfate was simultaneously administered iv to protect against cisplatin-induced nephrotoxicity. While only one of 18 patients (6%) with bulky residual ovarian carcinoma experienced a partial remission, two of six evaluable patients with minimal residual disease experienced surgically defined complete remissions. Local abdominal pain was often severe with the higher dose of bleomycin and was occasionally a problem with the lower dose schedule. Fever was common (greater than 70% of courses), but was reduced in degree by pretreatment with steroids. We conclude that combination ip chemotherapy with this three-drug regimen can result in objective tumor regressions and surgically defined complete remissions in patients with minimal residual ovarian carcinoma who have failed to achieve a complete remission following cisplatin-based iv chemotherapy.

Abdominal Neoplasms↗
PubMed1986

Continuous infusion of T101 monoclonal antibody in chronic lymphocytic leukemia and cutaneous T-cell lymphoma.

We report results of 24-h continuous infusions of murine monoclonal antibody T101 in six patients with chronic lymphocytic leukemia (CLL), and 10 with cutaneous T-cell lymphoma (CTCL), at doses of 10, 50, 100, or 500 mg. Similar side-effects were seen in CLL and CTCL, including direct toxic effects of therapy, such as fever, sweats, and chilling, and a 30% frequency of allergic manifestations. In vivo binding of T101 to target cells in blood, skin, lymph nodes, tumor masses, and bone marrow was demonstrated. Antigenic modulation occurred rapidly in all cases, and persisted throughout the infusion period. Peak serum T101 levels for equivalent doses were somewhat higher, and persisted longer in CTCL, perhaps because of differences in the number of circulating target cells. Antimouse antibodies were demonstrated in 5 of 10 CTCL vs. 0 of 6 CLL patients. In all five cases, there was a substantial component of T101 specificity in the antimouse response. Brief objective clinical responses were observed in 4 of 10 CTCL and 2 of 6 CLL patients. Acute anti-tumor effects of T101 were substantially more dramatic in CTCL than CLL, but appeared limited by antigenic modulation and the emergence of antimouse antibodies. In view of the in vivo binding and modulation, more durable anti-tumor effects may be achievable with cytotoxic immunoconjugates of this monoclonal antibody.

Antibodies, Monoclonal↗
PubMed1986

Response of paraneoplastic syndromes to antineoplastic therapy.

The development of a clinically apparent paraneoplastic syndrome in a patient with malignant disease is cause for considerable concern as the symptoms can be as serious and difficult to deal with as those produced by the cancer itself. While the information in the medical literature concerning the response of paraneoplastic processes to specific antineoplastic therapy is limited, case reports and small series would suggest that a number of syndromes are alleviated with successful treatment of the underlying neoplasm. As treatment programs for advanced malignant disease improve, a larger percentage of patients suffering from the effects of paraneoplastic processes will benefit from therapy directed at their cancer.

Dermatomyositis↗