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Biomedical subjects

M Markman

Publications and source records attributed to M Markman.

At least 199 records · Page 11Linked to original sources
PubMed1993

Evidence supporting the superiority of intraperitoneal cisplatin compared to intraperitoneal carboplatin for salvage therapy of small-volume residual ovarian cancer.

PURPOSE: To examine the relative efficacy of cisplatin-based intraperitoneal (IP) therapy versus carboplatin-based IP therapy as salvage treatment of small-volume residual ovarian cancer. PATIENTS AND METHODS: We retrospectively examined the surgically defined response rates of patients with ovarian cancer treated at the Memorial Sloan-Kettering Cancer Center on four organoplatinum-based salvage IP trials (cisplatin/etoposide, cisplatin/cytarabine, carboplatin/etoposide, carboplatin/etoposide + recombinant human erythropoietin). Additional criteria for inclusion in this analysis were: (a) small-volume residual disease (microscopic disease only or largest residual tumor mass < or = 0.5 cm) when IP therapy was initiated; (b) prior response to organoplatinum-based systemic therapy; (c) laparotomy evaluation for response to the IP salvage program. RESULTS: The surgically documented complete response rate for patients with microscopic disease treated with cisplatin-based or carboplatin-based therapy was 46% (6/13) versus 38% (6/16), respectively (P > 0.25). In contrast, the surgically documented overall and complete response rates for patients with small-volume macroscopic disease treated with cisplatin or carboplatin were 71% (12/17) versus 32% (6/19) (P < 0.05, chi 2 test with Yates' correction), and 41% (6/17) versus 11% (2/19) (p < 0.1), respectively. CONCLUSION: In agreement with experimental data demonstrating that the concentration of platinum within tumor is higher following equimolar doses of cisplatin, compared to carboplatin, we have observed, in this retrospective analysis, a higher surgically documented response rate for patients with small-volume residual macroscopic ovarian cancer receiving salvage cisplatin-based IP therapy. While a randomized trial will be required to definitively address the question of the relative effectiveness of the two commercially available organoplatinum agents for IP treatment of ovarian cancer, our data suggest that cisplatin is the superior agent for regional therapy in this disease.

Carboplatin↗
PubMed1993

Salvage intraperitoneal therapy of ovarian cancer employing cisplatin and etoposide: a Gynecologic Oncology Group study.

BACKGROUND: To further explore the potential of salvage intraperitoneal cisplatin-based therapy in patients with small-volume residual ovarian cancer a Phase II trial was conducted by the Gynecologic Oncology Group. METHODS: Ninety-two patients entered into this trial were treated with a regimen of cisplatin (100 mg/m2) and etoposide (200 mg/m2) delivered intraperitoneally every 4 weeks for a maximum of six cycles. RESULTS: Of the 84 patients evaluable for toxicity, grades 3-4 neutropenia, thrombocytopenia, neurotoxicity, and nephrotoxicity were observed in 25, 12, 6, and 9% of patients, respectively. A total of 41 patients were evaluable for response to the treatment program. Of the 25 evaluable patients with favorable pretreatment characteristics (prior response to systemic cisplatin or relapse > 6 months after completing initial chemotherapy), 10 (40%) achieved a surgically documented response (S-R), including 6 (24%) who achieved a surgically documented complete response (S-CR). Of the 16 patients with unfavorable pretreatment characteristics (less than a partial response to systemic cisplatin or a response of < 6 months duration) the S-R rate was only 12% (S-CR: 6%). CONCLUSIONS: In this large multi-institutional cooperative group study, we have confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer who have favorable pretreatment characteristics. The overall impact of these responses on disease-free and overall survival remains to be defined.

Adenocarcinoma↗
PubMed1993

Salvage therapy in ovarian cancer: is there a role for intraperitoneal drug delivery?

Phase 2 trials employing several antineoplastic agents have demonstrated that surgically documented responses, including complete responses, can result when patients with ovarian cancer are treated by the intraperitoneal route in the salvage setting following initial systemic chemotherapy. Activity is essentially limited to patients with very small-volume residual disease (microscopic cancer or largest visible tumor masses < or = 0.5 cm in maximum diameter) when the salvage regional therapy program is initiated. In the absence of a randomized phase 3 trial, the ultimate impact of these surgically documented responses on survival is difficult to evaluate, although long-term disease-free survival (> 4 years) has been demonstrated following intraperitoneal therapy in this clinical setting.

Antineoplastic Agents↗
PubMed1993

Diethyldithiocarbamate chemoprotection of carboplatin--induced hematological toxicity.

Carboplatin therapy has a more favorable toxicity profile than cisplatin and, given in appropriate doses, is equivalent in efficacy to cisplatin for suboptimal ovarian cancer. However myelosuppression frequently curtails therapy with carboplatin. Diethyldithiocarbamate (DDTC) is a thiol compound and heavy-metal-chelating agent that has been shown to protect against carboplatin-induced bone marrow suppression in animal models. This pilot study was undertaken to evaluate the ability of DDTC to ameliorate the degree and/or duration of myelosuppression from carboplatin chemotherapy in patients with relapsed ovarian cancer. Ten patients who had previously demonstrated a response to platinum-based chemotherapy, were treated with single-agent intravenous carboplatin 400 mg/m2 administered over 30-60 min every 4 weeks. Patients received their first cycle of carboplatin without DDTC, and their second cycle with DDTC. DDTC at 600 mg/m2 was infused over 3 h commencing 30 min prior to carboplatin and was well tolerated. Treatment with DDTC did not decrease the degree of leukopenia or thrombocytopenia associated with carboplatin chemotherapy, nor did it decrease the duration of myelosuppression. This clinical study demonstrates no evidence of a bone-marrow-protective effect for this dose and schedule of DDTC in patients receiving carboplatin chemotherapy.

Adenocarcinoma, Papillary↗
PubMed1993

Phase II trial of zeniplatin (CL 286,558), a new patinum compound, in patients with advanced ovarian cancer previously treated with organoplatinum-based therapy.

There is a critical need to find new chemotherapeutic agents that are active in platinum-refractory ovarian cancer. A phase II trial of zeniplatin (CL 286,558), a third-generation platinum compound, was conducted in 31 patients with advanced ovarian cancer to examine the safety and activity of the agent when used as a salvage treatment in individuals previously exposed to organoplatinum-based therapy. In general the drug was well tolerated, with moderate emesis and bone marrow suppression being observed in most patients. An unexpected side-effect was significant fever, of unknown etiology, which was noted in 16% of patients. Out of 20 patients, 2 (10%; 95% confidence intervals: 1%-32%) with clinically defined platinum-refractory disease achieved a partial response. Unfortunately, although we have defined definite but modest activity for zeniplatin in platinum-refractory ovarian cancer, further development of this drug has been discontinued because of the severe renal toxicity observed in other clinical trials of this cytotoxic agent.

Adult↗