The oral kinase inhibitor capivasertib (Truqap – AstraZeneca), a first-in-class AKT inhibitor, has been approved by the FDA for use in combination with the selective estrogen receptor degrader (SERD) fulvestrant (Faslodex, and generics) for treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer in adults with one or more PIK3CA/AKT1/PTEN-alterations who had disease progression on at least one endocrine-based regimen for metastatic disease or recurrence on or within 12 months of completing adjuvant therapy.

The oral poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (Lynparza – AstraZeneca) has been approved by the FDA for adjuvant treatment of adults with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative, high-risk early breast cancer who received prior neoadjuvant or adjuvant chemotherapy. The drug was previously approved for treatment of adults with deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer who received chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.

The oral cyclin-dependent kinase (CDK) 4/6 inhibitor abemaciclib (Verzenio – Lilly) has been approved by the FDA for use in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for adjuvant treatment of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence.1It was previously approved for the same indication, but patients were also required to have a Ki-67 score ≥20%. About 70% of all breast cancers are HR-positive and HER2-negative. Ki-67 is a prognostic biomarker for tumor proliferation; a score ≥20% is associated with early recurrence and poor prognosis.

Fam-trastuzumab deruxtecan-nxki (Enhertu – Daiichi Sankyo/AstraZeneca), which received accelerated approval by the FDA in 2019 for treatment of HER2-positive breast cancer based on its rate and duration of response,1 has been granted regular approval for treatment of adults with unresectable or metastatic HER2-positive breast cancer who received a prior anti-HER2-based regimen in the metastatic setting or in the neoadjuvant or adjuvant setting and developed recurrence during or within 6 months of completing treatment.

The FDA has approved elacestrant (Orserdu – Stemline), an oral estrogen receptor antagonist, for treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer in postmenopausal women or men who had disease progression following endocrine therapy. Elacestrant is the first oral selective estrogen receptor degrader (SERD) to be approved for treatment of breast cancer; the injectable SERD fulvestrant (Faslodex, and generics) was approved more than 20 years ago.

Sacituzumab govitecan-hziy (Trodelvy – Gilead) has been approved for treatment of unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in adults who received prior endocrine therapy and ≥2 additional systemic therapies for metastatic disease. It was previously approved for treatment-refractory metastatic triplenegative breast cancer and for treatment of locally advanced or metastatic urothelial cancer in adults who received platinum-based chemotherapy and a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.

The FDA has approved margetuximab-cmkb (Margenza – MacroGenics), a HER2/neu receptor antagonist, for use in combination with chemotherapy for treatment of metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer in adults who received ≥2 prior anti-HER2 regimens, at least one of which was for metastatic disease.

The oral tyrosine kinase inhibitor neratinib (Nerlynx – Puma Biotechnology) has been approved by the FDA for use in combination with capecitabine (Xeloda, and generics) for treatment of advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer in adults who received ≥2 prior anti-HER2-based regimens for metastatic disease. It was previously approved for use as monotherapy for extended adjuvant treatment of adults with early-stage, HER2-positive breast cancer following adjuvant trastuzumab (Herceptin)-based therapy. HER2 is overexpressed in about 20% of breast cancers. Up to 30% of early-stage, HER2-positive breast cancer cases treated with trastuzumab-based adjuvant therapy recur. Neratinib is the only HER2-directed small molecule approved for treatment of early-stage and metastatic HER2-postive breast cancer.

The oral cyclin-dependent kinase (CDK) 4/6 inhibitor abemaciclib (Verzenio – Lilly), which was approved by the FDA in 2017 for treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer, has now been approved for use in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for adjuvant treatment of patients with HR-positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score ≥20%.

The FDA has approved a fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase (Phesgo – Genentech) for use in combination with chemotherapy for neoadjuvant (preoperative) treatment of human epidermal growth factor receptor 2 (HER2)-positive, locally advanced, inflammatory, or early-stage breast cancer, or for adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence, or with docetaxel for treatment of those with HER2-positive metastatic breast cancer who have not received anti-HER2 therapy or chemotherapy for metastatic disease. Phesgo is the first combination that contains pertuzumab and trastuzumab for SC administration. IV pertuzumab (Perjeta) and IV and SC trastuzumab (Herceptin, and others) have been available for years for treatment of HER-2 positive breast cancer.

The FDA has approved sacituzumab govitecan-hziy (Trodelvy – Immunomedics), a trophoblast cell-surface antigen-2 (Trop-2)-directed antibody and topoisomerase inhibitor conjugate, for treatment of adults with metastatic triple-negative breast cancer who have received ≥2 prior therapies for metastatic disease. It is the first Trop-2-directed antibody-drug conjugate to become available in the US.

The FDA has approved two new drugs for treatment of previously-treated unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer: fam-trastuzumab deruxtecannxki (Enhertu – Daiichi-Sankyo/AstraZeneca), an IV HER2-directed monoclonal antibody linked to the topoisomerase I inhibitor DXd, and tucatinib (Tukysa – Seagen), an oral tyrosine kinase inhibitor.

Interim results of a double-blind, placebo-controlled trial suggest that off-label use of the anticholinergic drug oxybutynin may reduce the frequency and severity of hot flashes in women with breast cancer. Extended-release oral oxybutynin (Ditropan XL, and generics) has been shown to reduce the frequency and severity of hot flashes in healthy menopausal women.

Intrauterine devices (IUDs) and the etonogestrel implant are the most effective reversible contraceptive methods available. Hormonal oral contraceptives, patches, rings, and injectables are also highly effective in preventing pregnancy. When used alone, barrier and fertility-based methods generally have higher failure rates than other methods.

The FDA has approved the oral tyrosine kinase inhibitor neratinib (Nerlynx – Puma Biotechnology) for extended adjuvant treatment of adults with early-stage, human epidermal growth factor receptor 2 (HER2)-positive breast cancer, following adjuvant trastuzumab (Herceptin)-based therapy. HER2 is overexpressed in about 20% of breast cancers. Up to 30% of early-stage, HER2-positive breast cancer cases treated with trastuzumab-based adjuvant therapy recur.

The FDA has approved abemaciclib (Verzenio – Lilly), an oral cyclin-dependent kinase (CDK) 4/6 inhibitor, for treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. Abemaciclib is the third CDK 4/6 inhibitor to be approved in the US for this indication.

The oral cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib (Kisqali – Novartis) has been approved by the FDA for use in combination with an aromatase inhibitor for first-line endocrine-based therapy in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. Ribociclib is also available copackaged with the aromatase inhibitor letrozole (Femara, and generics) as Kisqali Femara Co-Pack. Ribociclib is the second CDK 4/6 inhibitor to be approved in the US for this indication; palbociclib (Ibrance) was the first. Abemaciclib (Verzenio), a third CDK 4/6 inhibitor, was recently approved and will be reviewed in a future issue.

The FDA has approved the pyrimidine analog uridine triacetate (Vistogard – Wellstat Therapeutics) for emergency treatment of a fluorouracil (5-FU) or capecitabine (Xeloda, and generics) overdose or severe toxicity that occurs within 96 hours following administration of one of these drugs. Fluorouracil is a cytotoxic antimetabolite used to treat breast, colorectal, and other cancers; capecitabine is an oral prodrug of fluorouracil.

Uridine triacetate, a prodrug, is deacetylated to uridine after oral administration. Excess circulating uridine is converted into uridine triphosphate, which inhibits the cytotoxic activity of 5-fluorouridine triphosphate, a fluorouracil metabolite, by competing with it for incorporation into RNA.

FDA approval was based on two unpublished open-label studies (summarized in the package insert) in a total of 135 adults and children with overdoses of fluorouracil or capecitabine (n=117) or severe or life-threatening toxicities within 96 hours after their administration (n=18). The overall survival rate at 30 days was 96%. In retrospective case reports that included 25 patients who received only supportive care after a fluorouracil overdose, the survival rate was 16%.

Vistogard is supplied as orange-flavored oral granules in single-dose packets containing 10 grams of uridine triacetate. The granules should be mixed with 3-4 ounces of soft food and taken every 6 hours for 20 doses. The recommended dose is 10 grams for adults and 6.2 grams/m² (10 grams maximum) for children. Mild to moderate nausea, vomiting, and diarrhea have been reported. The cost for one course of treatment is $75,000.1

1. Approximate WAC. WAC = wholesaler acquisition cost or manufacturer's published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price. Source: AnalySource® Monthly. June 5, 2016. Reprinted with permission by First Databank, Inc. All rights reserved. ©2016. www.fdbhealth.com/policies/drug-pricing-policy.

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Antimicrobial prophylaxis can decrease the incidence of postoperative surgical site infection after some procedures. Since the last Medical Letter article on this subject, consensus guidelines have been published. Recommendations for prophylaxis in specific surgical procedures are listed in Table 1.

The anthracycline doxorubicin with or without the alkylating agent ifosfamide is the standard first-line treatment for advanced soft-tissue sarcomas. The FDA recently approved the minor groove DNA intercalator trabectedin (Yondelis – Janssen) for treatment of unresectable or metastatic liposarcoma or leiomyosarcoma in patients previously treated with an anthracycline. Trabectedin has been available for years in Europe for treatment of advanced soft-tissue sarcoma. The FDA has also approved the microtubule inhibitor eribulin mesylate (Halaven – Eisai), which was approved earlier for treatment of metastatic breast cancer,1 for treatment of unresectable or metastatic liposarcoma, but not for leiomyosarcoma, in patients previously treated with an anthracycline.

Trabectedin binds guanine residues in the minor groove of DNA, which inhibits active transcription and blocks DNA repair proteins to achieve an antiproliferative effect.2 It has not been shown to be superior to doxorubicin for first-line treatment of advanced soft-tissue sarcomas,3 but has shown activity in anthracycline- and alkylating agent-resistant soft tissue sarcomas.4 FDA approval of trabectedin was based on a randomized, open-label trial comparing it to dacarbazine in 518 heavily pretreated patients with metastatic or recurrent leiomyosarcoma or liposarcoma. Median progression-free survival was significantly longer with trabectedin (4.2 months vs 1.5 months with dacarbazine). Median overall survival, however, was not significantly different (12.4 months with trabectedin vs 12.9 months with dacarbazine).5 Adverse effects of trabectedin include nausea, fatigue, neutropenia, and transient hepatic enzyme elevations.6 Trabectedin is administered over 24 hours through a central venous line every 3 weeks until disease progression or unacceptable toxicity occurs.

Eribulin mesylate is a microtubule-polymerizing drug that sequesters tubulin into nonfunctional aggregates.7 FDA approval of eribulin for treatment of advanced liposarcoma was based on a randomized, open-label trial comparing it to dacarbazine in 452 patients with unresectable or metastatic liposarcoma or leiomyosarcoma previously treated with an anthracycline. Median progression-free survival was 2.6 months in both groups, but overall survival was significantly longer with eribulin (13.5 months vs 11.5 months with dacarbazine). A pre-planned subgroup analysis found that the benefit was limited to patients with liposarcoma.8 Eribulin is the first drug shown to prolong overall survival in patients with advanced liposarcoma. The incidence of grade 3 or 4 adverse effects, particularly leukopenia and neutropenia, was higher with eribulin (67%) than with dacarbazine (56%). Fatigue, alopecia, peripheral neuropathy, nausea, and constipation also occurred. Eribulin is administered IV over 2 to 5 minutes on days 1 and 8 of a 3-week cycle.

1. Eribulin mesylate (Halaven) for breast cancer. Med Lett Drugs Ther 2011; 53:30.
2. AK Larsen et al. Unique features of trabectedin mechanism of action. Cancer Chemother Pharmacol 2015; 77:663.
3. B Bui-Nguyen et al. A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma: the TRUSTS trial. Eur J Cancer 2015; 51:1312.
4. BJ Petek et al. Trabectedin in soft tissue sarcomas. Mar Drugs 2015; 13:974.
5. GD Demetri et al. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol 2016; 34:786.
6. C Leporini et al. A comprehensive safety evaluation of trabectedin and drug-drug interactions of trabectedin-based combinations. BioDrugs 2014; 28:499.
7. NF Dybdal-Hargreaves et al. Eribulin mesylate: mechanism of action of a unique microtubule-targeting agent. Clin Cancer Res 2015; 21:2445.
8. P Schöffski et al. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet 2016 February 10 (epub).

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The FDA has approved filgrastim-sndz (Zarxio – Sandoz), a biosimilar of the recombinant human granulocyte colony-stimulating factor filgrastim (G-CSF; Neupogen), which has been available in the US since 1991. Zarxio is the first biosimilar product to be approved in the US; it has been available in Europe as Zarzio since 2009.

Palbociclib (Ibrance – Pfizer), an oral cyclin-dependent kinase inhibitor, has been approved by the FDA for use in combination with the aromatase inhibitor letrozole (Femara, and generics) for first-line treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. It is the first cyclin-dependent kinase inhibitor to become available in the US.

The FDA has approved the neoadjuvant (preoperative) use of pertuzumab (Perjeta – Genentech) in combination with trastuzumab (Herceptin) and docetaxel (Taxotere, and generics) for treatment of locally advanced, inflammatory, or early-stage HER2 (human epidermal growth factor receptor 2)-positive breast cancer patients with tumors >2 cm in diameter or node-positive disease. Pertuzumab in combination with trastuzumab and docetaxel was approved earlier for treatment of HER2-positive metastatic breast cancer. Pertuzumab is the first drug to be approved for neoadjuvant treatment of breast cancer.

The FDA has approved a low-dose formulation of the selective serotonin reuptake inhibitor (SSRI) paroxetine mesylate (Brisdelle – Noven Therapeutics) for treatment of moderate-to-severe vasomotor symptoms associated with menopause. It is the first non-hormonal therapy to be approved for this indication. Paroxetine mesylate (Pexeva) and paroxetine hydrochloride (Paxil, and generics) are marketed in higher doses for treatment of depression and other psychiatric disorders.

Ado-trastuzumab emtansine (Kadcyla – Genentech), a human epidermal growth factor receptor 2 (HER2)-targeted antibody and microtubule inhibitor conjugate, has been approved by the FDA for intravenous (IV) treatment of HER2-positive metastatic breast cancer in patients previously treated with trastuzumab (Herceptin) and a taxane. The prefix was added to the new conjugate’s name at the request of the FDA to distinguish it from trastuzumab.

Use of screening tests to identify cancers before they cause symptoms can lead to earlier therapy and may improve outcomes. Screening tests for some common cancers are reviewed below.

Pertuzumab (Perjeta – Roche/Genentech), a humanized monoclonal antibody, has been approved by the FDA for use in combination with trastuzumab (Herceptin) and docetaxel (Taxotere, and others) for first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.

Three retrospective studies have recently reported an association between beta-blocker use and a reduction in breast cancer metastasis and recurrence. No prospective, randomized trials have been published.

Adjuvant hormone therapy with anti-estrogen drugs has been shown to reduce disease recurrence and mortality in postmenopausal women with estrogen receptor (ER)-positive breast cancer. In recent years, aromatase inhibitors (AI) have become the preferred first-line hormonal treatment over tamoxifen for such patients.1,2

A randomized, placebo-controlled, double-blind trial of exemestane (Aromasin, and others) in postmenopausal women considered at increased risk for breast cancer found that the aromatase inhibitor, over a median follow-up of 35 months, significantly decreased the annual incidence of invasive breast cancer from 0.55% to 0.19% (PE Goss et al. N Engl J Med, epub June 4, 2011).

Eribulin mesylate (Halaven – Eisai) has been approved by the FDA for treatment of patients with metastatic breast cancer who have previously received at least 2 chemotherapy regimens for metastatic cancer. Prior therapy should have included an anthracycline and a taxane in either an adjuvant or metastatic setting. Other drugs used to treat anthracycline- and taxane-refractory metastatic breast cancer include capecitabine (Xeloda), gemcitabine (Gemzar, and others) and vinorelbine (Navelbine, and others).

Conflicting recommendations on when to screen for breast cancer are problematic for healthcare providers. The recent recommendation by the US Preventive Services Task Force (USPSTF) against routine screening mammography for women 40-49 years old conflicts with recommendations made by other organizations such as the American Cancer Society and earlier recommendations made by the USPSTF in 2002.

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Use of a selective serotonin reuptake inhibitor (SSRI) is common in women taking tamoxifen (Nolvadex, and others) for breast cancer, both to treat depression and to decrease hot flashes. However, tamoxifen must be metabolized by CYP2D6 to become pharmacologically fully active (MJ Higgins et al. J Natl Compr Canc Netw 2009; 7:203), and the SSRIs fluoxetine (Prozac, and others) and paroxetine (Paxil, and others) are strong inhibitors of CYP2D6. Sertraline (Zoloft, and others) inhibits CYP2D6 to a lesser extent. Citalopram (Celexa, and others) and escitalopram (Lexapro), the 2 other SSRIs approved for treatment of depression, are only weak inhibitors of CYP2D6.

Two observational studies presented at a recent meeting of the American Society of Clinical Oncology (45th annual meeting, May 29-June 2, 2009, Orlando, FL abstracts CRA508, CRA509) examined the effect of strong inhibitors of CYP2D6 on the success rate of tamoxifen in preventing recurrence of breast cancer. One found that women who took fluoxetine, paroxetine or sertraline (or bupropion, duloxetine, terbinafine, quinidine or long-term diphenhydramine) with tamoxifen had a higher 2-year recurrence rate (13.9% vs. 7.5%). The other study found no association between cancer recurrence and use of a CYP2D6 inhibitor.

There is no good evidence that any one SSRI is more effective than any other for treatment of depression. For women who are taking tamoxifen and need to begin treatment with an SSRI to treat depression, citalopram or escitalopram might be the safest choice (Treat Guidel Med Lett 2006; 4:35). Use of an SSRI to treat hot flashes in women taking tamoxifen should probably be reconsidered.

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Osteoporosis is characterized by low bone mass with microarchitectural disruption and skeletal fragility that results in an increased risk of fracture. The diagnosis has traditionally been established by bone densitometry, which is generally reported in terms of standard deviations (SD) from mean values in young adults (T score). The World Health Organization (WHO) has defined normal bone mineral density (BMD) for women as a value within one SD of the young adult mean. Values 2.5 SD (T score -2.5) or more below the mean are defined as osteoporosis. The WHO has developed a computerized model (FRAX) that predicts the 10-year probability of hip fracture based on clinical risk factors and BMD at the femoral neck.

Bevacizumab (Avastin - Genentech) is a recombinant humanized monoclonal antibody that binds to vascular endothelial growth factor and prevents it from binding to receptors on endothelial cells, inhibiting formation of new blood vessels. Previously approved by the FDA for use in combination regimens for first-line treatment of metastatic colon cancer and metastatic non-small cell lung cancer, and used off-label for treatment of agerelated macular degeneration, it has now also been approved by the FDA for use in combination with paclitaxel (Taxol, and others) for first-line treatment of HER2-negative metastatic breast cancer.

Ixabepilone (ix ab ep' i lone; Ixempra - Bristol-Myers Squibb), a semisynthetic epothilone analog, has been approved by the FDA for treatment of advanced breast cancer. It is indicated for use in combination with capecitabine (Xeloda - Roche) for treatment of locally advanced or metastatic breast cancer after failure of an anthracycline such as doxorubicin (Adriamycin) and a taxane such as paclitaxel (Taxol, and others). It is also approved as monotherapy for treatment of metastatic or locally advanced breast cancer after an anthracycline, a taxane and capecitabine have failed.

Direct-to-consumer advertisements are urging women to be tested for mutations in BRCA1 and BRCA2 genes, which are the most common known causes of an inherited predisposition to breast and ovarian cancer. Clinically important BRCA mutations have been found in about 2% of Ashkenazi Jewish women, and are estimated to occur in about 1 in 300 to 500 women in the general non-Jewish US population. The prevalence appears to be lower in non-whites.

Lapatinib (Tykerb - GlaxoSmithKline), an oral inhibitor of both HER-2 and epidermal growth factor receptor type 1 (EGFR-1 or ErbB-1), has been approved by the FDA for use in combination with capecitabine (Xeloda) to treat advanced or metastatic breast cancer that overexpresses HER-2 in patients who have received prior therapy that included an anthracycline, a taxane and trastuzumab (Herceptin), an intravenous monoclonal antibody that also inhibits HER-2.

Preliminary results from a new study, unpublished but reported in a press release from the National Cancer Institute and widely disseminated in the public press, suggest that raloxifene (Evista) might be a better choice than tamoxifen (Nolvadex, and others) for prevention of breast cancer in high-risk postmenopausal women.

A new albumin-bound formulation of paclitaxel (Abraxane - American Pharmaceutical Partners) has been approved by the FDA for treatment of metastatic breast cancer after failure of combination chemotherapy or relapse within 6 months of adjuvant chemotherapy. This formulation is free of polyoxyethylated castor oil (Cremophor), a solvent thought to contribute to the hypersensitivity reactions that occur frequently with standard paclitaxel (Taxol, and others) and are severe in about 3% of patients.

In addition to surgery and radiation therapy, a variety of drugs are used both singly and in combination to treat breast cancer. This article summarizes the principles of adjuvant therapy and treatment for metastatic disease. A summary of individual drugs and their adverse effects begins on page 3.

Anastrozole (Arimidex - AstraZeneca, Medical Letter 1996; 38:61), an aromatase inhibitor, has received accelerated approval from the FDA for adjuvant treatment of postmenopausal women with early hormone-receptor-positive breast cancer. The drug was approved for treatment of postmenopausal women with metastatic breast cancer in 1996.

The tables in this article list drugs used for treatment of cancer in the USA and Canada and their major adverse effects. The choice of drugs in Table I is based on the opinions of Medical Letter consultants. Some drugs are listed for indications for which they have not been approved by the US Food and Drug Administration. In some cases, such as elderly patients or those with many co-morbid illnesses, the regimen of choice might not be suitable. For many of the cancers listed, surgery and/or radiation therapy may be the treatment of choice or may also be part of the management. Anticancer drugs and their adverse effects are listed in Table II on page 46. A partial list of brand names appears on page 52.

Fulvestrant (Faslodex -- AstraZeneca), an estrogen receptor antagonist given intramuscularly (IM) once a month, was recently approved by the FDA for treatment of hormone-receptor-positive metastatic breast cancer in postmenopausal women with disease progession on tamoxifen (Nolvadex, and others) or another antiestrogen.

Docetaxel (Taxotere - Rh ne-Poulenc Rorer), a semisynthetic taxoid similar to paclitaxel (Taxol - Medical Letter, 35:39, 1993), has been approved by the US Food and Drug Administration for use in locally advanced or metastatic breast cancer that has progressed or relapsed during treatment that included an anthracycline such as doxorubicin (Adriamycin, and others).

Anastrozole (Arimidex - Zeneca), a selective nonsteroidal aromatase inhibitor, has been approved by the US Food and Drug Administration (FDA) for treatment of postmenopausal women with advanced breast cancer that has progressed during treatment with tamoxifen (Nolvadex, and others).

The prognosis in breast cancer is generally poor for women with unresectable, locally advanced disease (inflammatory cancer or more than 10 positive lymph nodes) and for those with metastases. Autologous bone marrow transplantation - removing bone marrow from multiple sites under general anesthesia, giving high-dose chemotherapy with or without total body radiation, and reinfusing the bone marrow intravenously - is being tried in some of these patients.

The most important prognostic variable in early breast cancer is axillary lymph node involvement. Based on past experience, after 10 years about 70% of node-negative patients will be alive and apparently free of disease; about 30% will have relapsed or died. Patients with positive nodes may have a 30% to 60% relapse rate, depending on the number of positive nodes and other prognostic factors, such as the presence of estrogen receptors (IC Henderson et al, in VT DeVita, Jr et al, eds, Cancer: Principles and Practice of Oncology, 3rd ed, Philadelphia:Lippincott, 1989, p 1197). Which of these patients should receive adjuvant treatment with cytotoxic drugs and/or endocrine therapy is controversial; a National Cancer Institute (NCI) Consensus Conference on this subject is scheduled for June.