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Biomedical subjects

M Markman

Publications and source records attributed to M Markman.

At least 163 records · Page 9Linked to original sources
PubMed1995

Intraperitoneal paclitaxel in the management of ovarian cancer.

For several reasons, including its demonstrated activity in ovarian cancer, large size, hepatic metabolism, and lack of vesicant properties, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is an interesting agent to consider for intraperitoneal administration in the management of ovarian cancer. Two phase I trials have confirmed a major pharmacokinetic advantage (> or = 1,000-fold) for peritoneal cavity exposure compared with the systemic compartment following intraperitoneal delivery of paclitaxel. A Gynecologic Oncology Group phase II trial of second-line intraperitoneal paclitaxel in ovarian cancer patients is currently in progress to determine whether the high concentrations and prolonged duration of exposure to paclitaxel of the surface of the peritoneal cavity can be translated into increased tumor cell kill and objective responses in this clinical setting. Future development of this novel therapeutic strategy will depend on the results of this important clinical trial.

Antineoplastic Agents, Phytogenic↗
PubMed1995

The use of chemotherapy as palliative treatment for patients with advanced ovarian cancer.

Despite the high objective response rate of ovarian cancer to several reported platinum-based combination chemotherapy regimens, the majority of patients with advanced disease ultimately require consideration of a salvage regimen delivered for palliation of symptoms. A number of therapeutic strategies have been used in such patients, including re-treatment with cisplatin or carboplatin, or the use of paclitaxel, ifosfamide, hexamethylmelamine, oral etoposide, 5-fluorouracil plus leucovorin, or tamoxifen. Multiple factors and individual clinical features of the patient must be considered when selecting the most appropriate salvage therapy to be used in this clinical setting.

Antineoplastic Agents↗
PubMed1995

Surgery for support and palliation in patients with malignant disease.

Surgery is the major curative treatment modality for patients with malignant disease. However, surgery also plays an important role in supportive and palliative care of cancer patients. In settings in which maintaining quality of life rather than prolongation of survival is the major goal of treatment, the potential morbidity of more extensive surgical procedures must be carefully weighed against their possible benefits, and alternative options (if available and appropriate) should be carefully considered.

Humans↗
PubMed1995

Intraperitoneal paclitaxel: a possible role in the management of ovarian cancer?

Intraperitoneal paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been examined for a potential role in the management of ovarian cancer based on its (I) documented activity in ovarian cancer, (2) cycle-specific cytotoxicity, (3) large molecule, (4) at least partial metabolism in the liver, and (5) nonvesicant properties. Phase I evaluation has confirmed that the drug can be delivered safely intraperitoneally, with a major (> or = 3 log) pharmacokinetic advantage for peritoneal cavity exposure over that of the systemic compartment. Phase II and, ultimately, randomized phase III trials will be required to determine whether the tremendous pharmacokinetic advantage associated with regional delivery of paclitaxel can be translated into improved outcomes for women with advanced, but small-volume residual, ovarian cancer.

Clinical Trials as Topic↗
PubMed1995

Rationale for examining the combination of paclitaxel and ifosfamide in the treatment of advanced ovarian cancer.

Both paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and ifosfamide have been demonstrated to be active agents in patients with clinically defined platinum-refractory ovarian cancer. While there might be interest in combining these two drugs as salvage therapy for this disease, the recent inclusion of paclitaxel as initial therapy for advanced ovarian cancer, along with a platinum agent (cisplatin or carboplatin), makes it unlikely that paclitaxel and ifosfamide will be used clinically in this malignancy. However, if alkylating agents are not to be used as part of the initial chemotherapy strategy for women with advanced ovarian cancer, it will be important to evaluate the activity of ifosfamide as salvage therapy in individuals treated only with, and demonstrated to be refractory to, a platinum agent and paclitaxel. If significant activity for ifosfamide is observed in this clinical setting, evaluation of the potential utility of a three-drug combination regimen comprising ifosfamide, paclitaxel, and cisplatin or carboplatin may be quite relevant.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Simultaneous dose escalation and schedule intensification of carboplatin-based chemotherapy using peripheral blood progenitor cells and filgrastim: a phase I trial.

Our purpose was to determine the maximum tolerated dose of, and the minimum interval between treatments with, multiple cycles of carboplatin (CBDCA) rescued with peripheral blood progenitors and filgrastim. Eligible patients had advanced cancers without prior chemotherapy or radiotherapy. The study design involved a sequential cross-over in which patients initially received two or three courses of cyclophosphamide (CPA) at a dose of 3.0 g/m2, supported by filgrastim. Multiple leukaphereses were then performed during the rebound phase of hematological recovery following each CPA-induced nadir to harvest peripheral blood progenitors, which were then reinfused as rescue following each of four courses of CBDCA. We attempted to administer the CBDCA at 14-day intervals. The CBDCA dose (mg/m2/course) was escalated as follows in successive cohorts of patients: Level I, 500; Level II, 800; Level III, 1200; Level IIIa, 1000. Following determination of the maximum tolerated dose of CBDCA administered in this fashion, a subsequent cohort of patients (Level IV) were treated with two courses of high-dose CPA and four courses of the combination of CBDCA (1000 mg/m2) plus CPA (1500 mg/m2). Thirty-one patients were enrolled in the trial. Five patients were removed from study prior to completion of protocol therapy, three due to toxicity and two who developed progressive cancer while on study. The maximum tolerated dose of CBDCA was 1000 mg/m2, with dose-limiting ototoxicity occurring at 1200 mg/m2. The median inter-treatment interval for all cycles was 15 days (range, 12-30). The median intervals between CBDCA courses for each dose level were: Level I, 17 days; Level II, 17 days; Level III, 14 days; Level IIIa, 15 days; Level IV, 16 days. The median dose intensity of the CPA phase was 1493 mg/m2/week. The median (and range) CBDCA dose intensities (measured from the start of CBDCA) for each dose level were: I, 185 (151-222); II, 328 (305-380); III, 567 (512-646); IIIa, 465 (363-481); Level IV, 468 (333-500). Neutropenic fever complicated 35 of 113 CBDCA or CBDCA/CPA courses. Platelet transfusion was required in 51 of 113 courses. One patient had severe epistaxis. There were no treatment-related deaths. Among 27 patients with ovarian cancer who were evaluable for response, there were 5 pathologically documented complete (including 3 of 10 at Level IV) and 16 partial responses. We concluded that peripheral blood progenitors facilitate the simultaneous dose escalation and schedule intensification of carboplatin chemotherapy. The effect is sustained over four courses of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Follow-up of the asymptomatic patient with ovarian cancer.

At present the optimal follow-up/monitoring strategy for the asymptomatic patient with advanced ovarian cancer after initial treatment remains undefined. Important considerations in the decision to take a more "passive" or "active" approach in follow-up include: (1) absence of data on the overall clinical utility of second-line ("salvage") therapy in ovarian cancer; (2) costs, morbidity, and mortality of possible monitoring and treatment strategies; and (3) patient preference for a particular approach. Currently, it must be concluded that there is no evidence that intensive investigative monitoring efforts in the asymptomatic patient exert a significant positive impact on overall survival, symptom-free survival, or quality of life. However, in carefully selected patients, such a strategy may be an appropriate management option, as long as individuals followed in this manner are informed of the limited data demonstrating the value of either intensive monitoring or therapy in this clinical setting.

Adult↗