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Tate Thigpen

Publications and source records attributed to Tate Thigpen.

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The role of gemcitabine in first-line treatment of advanced ovarian carcinoma.

The combination of paclitaxel and carboplatin is now established as the standard first-line chemotherapy regimen for advanced ovarian cancer. Ways in which this standard therapy can be further improved are being investigated, and several approaches have been taken. One approach is to integrate a different cytotoxic agent into the standard combination. Gemcitabine is one such cytotoxic agent that is of particular interest because it has activity in disease resistant to treatment with paclitaxel plus carboplatin, and also has a different mechanism of action to that of the two agents in the standard combination. Gemcitabine plus cisplatin has shown activity in phase II trials and results are awaited from a phase III trial comparing paclitaxel plus carboplatin with gemcitabine plus carboplatin doublets. Using agents sequentially has been shown to be as effective as using them in combination; therefore, using a gemcitabine plus platinum doublet sequentially with paclitaxel plus carboplatin has also been studied. A phase III trial has closed and results are expected shortly. Triplet combinations have also been shown to be effective in early stage trials, although dose-limiting myelosuppression occurs with gemcitabine plus paclitaxel plus carboplatin. Two phase III trials of this triplet have finished and are awaiting data maturation. Lastly, a sequential triplet of gemcitabine plus paclitaxel plus carboplatin has been investigated, but high pulmonary toxicity led to the study being halted. The role of gemcitabine in first-line advanced ovarian cancer will become much clearer once the results from the various phase III trials are published.

Antineoplastic Combined Chemotherapy Protocols↗

First-line therapy for ovarian carcinoma: what's next?

Based on results from large, randomized trials conducted over the last 25 years, the current standard of care for newly diagnosed advanced (FIGO stage III-IV) ovarian carcinoma is surgical bulk reduction followed by six cycles of paclitaxel plus carboplatin. This approach has resulted in an enhanced response rate and clinical complete response rate, an improved progression-free survival, an increase in survival, and more long-term survivors. Despite these results, the overall frequency of relapse and hence need for second-line therapy is 62%. Ongoing and future studies focus or will focus on four major themes: dose intensity through the use of intraperitoneal chemotherapy in selected patients, addition of a third cytotoxic agent to front line therapy, addition of a targeted or biologic agent to front-line therapy, and the development of effective maintenance or consolidation therapy. The current standard of care for patients who present with limited (FIGO stage I-II) ovarian carcinoma is the use of prognostic factors to classify the patient as at low risk or high risk for recurrence. High risk features include: grade 2 or 3 disease, disease on the surface of the ovary, disease outside the ovary, positive peritoneal cytology, or the presence of ascites. Any one high risk feature makes the patient high risk for recurrence. Patients at low risk require surgical resection only, whereas those at high risk for recurrence require adjuvant therapy. Ongoing studies evaluate the duration of therapy and the potential value of anti-angiogenic agents in those patients at high risk for recurrence. Future directions point to the evaluation of targeted or biologic agents in high risk patients. At present, there is no evidence that any approach constitutes an effective screening test. Studies of serum markers, transvaginal sonography, and serum proteomic profiles have failed to establish any of these techniques as an effective tool for early diagnosis. An overview of current management and its basis will be followed by a discussion of the rationale for both current and potential future trials.

Antineoplastic Combined Chemotherapy Protocols↗

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Antineoplastic Combined Chemotherapy Protocols↗

The role of gemcitabine-based doublets in the management of ovarian carcinoma.

Efforts to improve further therapy for advanced ovarian carcinoma currently focus on addition of a third active agent to front-line chemotherapy. Three agents with activity against disease clinically resistant to paclitaxel and the platinum compounds are of greatest interest: gemcitabine, topotecan, and liposome-encapsulated doxorubicin. Three strategies to add a third agent include a triplet regimen that adds a third agent concurrently; a sequential doublet regimen giving three to four cycles of the new agent plus a platinum followed by three to four cycles of paclitaxel plus a platinum; and sequential single agents consisting of three to four cycles of the new agent with three to four cycles each of paclitaxel and a platinum. Gemcitabine in combination with another agent has been evaluated to develop doublet regimens for the second of these three strategies. Combinations both feasible and active include gemcitabine plus cisplatin or carboplatin, gemcitabine plus paclitaxel, gemcitabine plus topotecan, gemcitabine plus liposome-encapsulated doxorubicin, gemcitabine plus vinorelbine, and gemcitabine plus treosulfan. The combinations of gemcitabine plus a platinum compound appear most promising with synergism suggested by the data. A gemcitabine/carboplatin doublet for four cycles followed by four cycles of paclitaxel/carboplatin is currently under evaluation in a randomized phase III trial (Gynecologic Oncology Group [GOG] protocol 0182).

Antimetabolites, Antineoplastic↗

The role of chemotherapy in the management of carcinoma of the cervix.

Carcinoma of the cervix remains the most common form of cancer to affect women worldwide despite effective screening techniques. Advances in treatment, particularly systemic therapies, have improved outcomes for cervical cancer. This article examines the role of chemotherapy, particularly in those patients with disseminated disease and those with locally advanced disease in the pelvis.

Antineoplastic Combined Chemotherapy Protocols↗