Ovarian Cancer

The development of topotecan (Hycamtin) and the encouraging preliminary results of its use in clinical trials are comprehensively reviewed by Takimoto and Arbuck. The successful development of topotecan demonstrates that focused research and developmental efforts by the pharmaceutical industry in anticancer therapeutics can actually “pay off.” Approximately 15 years ago, the prototypic topoisomerase I inhibitor camptothecin was “placed back on the shelf” because it induced severe, unpredictable toxicity when administered as a sodium salt (sodium camptothecin). After recognition that camptothecin was active by virtue of a novel mechanism of action (topoisomerase I inhibition), developmental research efforts at SmithKline Beecham led to the synthesis of a myriad of camptothecin analogs, significant structure-function information, and the ultimate selection of topotecan as a lead camptothecin analog for clinical development.[1-3]

Immune responses are generated in a complex network of cellular and humoral factors. The complexity of this system makes it difficult to generate subsets of cells in vivo that are most effective against cancer cells. The goal of vaccine strategies is to redirect the immune system against cancer cells primarily by generating specific T-cell responses which would be the most effective anti-tumor effector cells.

The article by Drs. Takimoto and Arbuck reviews the chemistry, mechanism of action, pharmacology and clinical trials of topotecan (Hycamtin), one of two topoisomerase I inhibitors approved recently by the FDA. Topotecan was approved for refractory ovarian cancer and irinotecan (Camptosar) for advanced colorectal cancer. These drugs represent a new drug class designed to inhibit topoisomerase I, an enzyme involved in relaxation of torsional strain in supercoiled DNA allowing replication and translation. The authors’ overview is informative and unbiased.

Topotecan (Hycamtin) is a promising new topoisomerase I-targeting anticancer agent that first entered clinical trials in 1989 under National Cancer Institute sponsorship in collaboration with SmithKline Beecham. In 1996, it

Therapeutic and prophylactic vaccines that harness the potential of the immune system against a number of gynecologic cancers are now being developed. The therapeutic vaccines coerce the cellular components of the

The treatment of advanced pancreatic carcinoma has been viewed with pessimism. Because of the lack of activity of commonly used agents, there is no consensus regarding a standard chemotherapy regimen. Assessment of

Data from North American clinical trials have shown that vinorelbine (Navelbine) is well tolerated when used as a single agent for the treatment of non-small-cell lung cancer, advanced breast cancer, or ovarian cancer. Myelosuppression is the primary dose-limiting toxicity.

Liposomes have been proposed as potential vehicles for drug therapy targeted to solid tumors, in particular, because of the increased permeability of these tumors to macromolecules. The recent development of Stealth

While doxorubicin (Adriamycin) is among the most active single agents in the treatment of breast cancer and other solid tumors, its concomitant toxicity limits its use. Quality-of-life issues have driven the search for gentler,

Many of the more commonly observed adverse effects of standard doxorubicin (Adriamycin) are lessened by pegylated liposomal delivery (Doxil). The slow release of doxorubicin into normal tissue cells via this form of liposomal delivery ameliorates its potential for severe alopecia, nausea and vomiting, cardiotoxicity, and myelosuppressive toxicity. Infusion-related acute reactions are managed by slowing infusion rates and thorough dilution and mixing of the infused drug. Vesicant properties normally seen with doxorubicin are absent. Palmar-plantar erythrodysesthesia can be reduced by decreasing the dose or increasing the dosing interval. Many of these side effects are developing a predictable profile and are manageable. Because of its overall reduced toxicity profile, pegylated liposomal doxorubicin may be well-suited for use in combination chemotherapeutic regimens. [ONCOLOGY 11(Suppl 11):54-62, 1997]

After pegylated liposomal doxorubicin (PEG-LD) (Doxil) was shown to be active in ovarian tumors, several trials were developed at the University of Southern California to determine its safety and efficacy in a variety of gynecologic and peritoneal malignancies. Completed phase I and phase II trials have found PEG-LD to be safe and effective in the treatment of platinum- and paclitaxel-refractory epithelial ovarian carcinoma. A new phase II trial is currently underway in similarly refractory patients with ovarian and other related cancers and various degrees of pretreatment. In addition, the efficacy of PEG-LD is being explored in combination with paclitaxel (Taxol), with cisplatin, and with hyperthermia. [ONCOLOGY 11(Suppl 11):38-44, 1997]

Breast cancer is second only to lung cancer as a leading cause of cancer mortality in women. In women with metastatic, hence, essentially incurable disease, we strive to find effective chemotherapeutic regimens that offer a

SEATTLE-Targeted Genetics Corporation’s tumor suppressor gene product, tgDCC-E1A, is currently being tested in two phase I trials.

ROCKVILLE, Md-The Food and Drug Administration (FDA) has cleared Bristol-Myers Squibb’s Taxol (paclitaxel) Injection for use in the second-line treatment of AIDS-related Kaposi’s sarcoma (KS). Taxol is also approved for second-line use in metastatic breast and ovarian cancer.

Protogé, a first-of-its-kind software program that enables oncologiststo generate study protocols within a few hours rather than weeks, is now

BOCA RATON, Fla--Ovarian cancer survivors have formed the National Ovarian Cancer Coalition (NOCC), an organization whose main mission is to prevent deaths from ovarian cancer by advocating for the development of new techniques for early detection and by raising awareness levels about the disease.

NEW ORLEANS--Women seeking BRCA1 testing appear, as a group, to be more distressed and psychologically vulnerable than those who do not wish to be tested, according to two studies from Lombardi Cancer Center, Georgetown University, reported at the American Society of Preventive Oncology annual meeting. The women in the studies were at high risk because of a close family history of breast or ovarian cancer.

Although candidate genes for hereditary pancreatic cancer have been identified (Figure 1), namely p16 and BRCA2, pancreatic cancer patients having an inherited predisposition will not be easy to recognize on clinical grounds.

Despite a heightened focus of the medical and research community on prostate cancer, many important questions about this disease remain unanswered. These include questions about the possible prevention of prostate cancer, as well as the optimal treatment approaches for localized, locally advanced, metastatic, and hormone-refractory disease. A whole host of prospective, well-designed clinical trials are currently in progress that should answer many of these questions. This review briefly explores some of these unresolved issues and describes ongoing trials designed to address them. [ONCOLOGY 11(8):1-11, 1997]

Preclinical studies show that docetaxel (Taxotere) and cyclophosphamide (Cytoxan, Neosar) are synergistic against MA 13/C mammary adenocarcinoma. Both agents are highly active as

ASCO--Use of the investigational resistance modulator PSC-833 in combination with paclitaxel (Taxol) is safe and appears to renew paclitaxel response in some patients with refractory advanced ovarian cancer, Abbie L. Fields, MD, said in an ASCO poster presentation of the preliminary results of the phase II study.

BETHESDA, Md--Women of Ashkenazi Jewish lineage appear to have a lower risk of breast and ovarian cancer from mutations in the BRCA1 and BRCA2 genes than was first thought, a study from the National Institutes of Health has found.

This special series on cancer and genetics is compiled and edited by Henry T. Lynch, MD, director of the Hereditary Cancer Institute, professor of medicine, and chairman of the Department of Preventive Medicine and Public Health, Creighton University School of Medicine, and director of the Creighton Cancer Center, Omaha, Nebraska. Part I of this three-part series on pancreatic cancer appeared in June 1997. Part II (below) reviews the gene mutations thought to contribute to the development of hereditary pancreatic cancer, and Part III will explores the clinical recognition of a hereditary predisposition to pancreatic cancer.

Radioimmunotherapy allows for the delivery of systemically targeted radiation to areas of disease while relatively sparing normal tissues. Despite numerous challenges, considerable progress has been made in the application of radioimmunotherapy to a wide variety of human malignancies. The greatest successes have occurred in the treatment of hematologic malignancies. Radioimmunotherapy, with or without stem-cell transplant support, has produced substantial complete remission rates in chemotherapy-resistant B-cell lymphomas. Nonmyeloablative regimens have shown so much promise that they are now being tested as initial therapy for low-grade B-cell lymphomas. Although solid tumor malignancies have been less responsive to radioimmunotherapy, encouraging results have been obtained with locoregional routes of administration, especially when the tumor burden is small. Greater tumor-to-normal tissue ratios are achievable with regional administration. Even with intraperitoneal and intrathecal administration, bone marrow suppression remains the dose-limiting toxicity. Ongoing research into new targeting molecules, improved chelation chemistry, and novel isotope utilization is likely to extend the applications of this strategy to other tumor types. The potential for radioimmunotherapy will be enhanced if this modality can be optimally adapted for integration with other agents and if the administration method can be tailored to the type and distribution of malignancy. [ONCOLOGY 11(7):979-987, 1997]

Theoretically, effective regional cancer chemotherapy should afford the opportunity to deliver a significantly higher concentration of a cytotoxic agent than is possible with systemic administration of the same agent. Furthermore, regional chemotherapy should cause its greatest stress on the site of administration, producing a lesser burden of toxicity on the whole body.