Cancer Treatment

Tamoxifen for breast pain

Tamoxifen can be used off-label to treat breast pain (mastalgia), because it reduces estrogen levels that cause breast swelling.In one study, tamoxifen relieved pain in more than two-thirds of women who had a history of severe breast pain. Experts disagree about the use of tamoxifen for breast pain, because it has important side effects and risks.

One double blind randomized comparatiove study(RCT)  compared tamoxifen 20 mg daily versus placebo. It found that significantly more women experienced pain relief (measured by visual analogue scale over 3 months) with tamoxifen compared with placebo (> 50% reduction in mean pain score: 22/31 [71%] with tamoxifen v 11/29 [38%] with placebo; P < 0.025). The second RCT (93 women) compared tamoxifen, danazol, and placebo. It found that significantly more women taking tamoxifen achieved a good outcome (> 50% reduction in mean pain score) at the end of treatment, 6 months later, and 12 months later, compared with placebo (> 50% reduction in pain score after 6 months of treatment: 23/32 [72%] with tamoxifen v 11/29 [38%] with placebo; P = 0.035). The third RCT (88 women, aged 22–44 years) found that 8 months of tamoxifen increased the proportion of women who achieved complete recovery (outcome not clearly defined) compared with placebo (40/44 [90%] with tamoxifen v 0/44 [0%] with placebo; P value not reported).

In conclusion, Tamoxifen is not licensed for mastalgia in the UK or USA. There is a consensus to limit its use to no more than 6 months at a time under expert supervision, and with appropriate non-hormonal contraception, because of the high incidence of adverse effects.

Fentiman IS (2004). Management of breast pain. In JR Harris et al., eds., Diseases of the Breast, 3rd ed., pp. 57–62. Philadelphia: Lippincott Williams and Wilkins.

Kontostolis E, Stefanidis K, Navrozoglou I, et al. Comparison of tamoxifen with danazol for treatment of cyclical mastalgia. Gynecol Endocrinol 1997;11:393–397. 

Fentiman IS, Caleffi M, Brame K, et al. Double-blind controlled trial of tamoxifen therapy for mastalgia. Lancet 1986;1:287–288. 

Grio R, Cellura A, Geranio R, et al. Clinical efficacy of tamoxifen in the treatment of premenstrual mastodynia. Minerva Ginecol 1998;50:101–103.   GEMB Group. Tamoxifen therapy for cyclical mastalgia: dose randomised trial. Breast 1997;5:212–213.

Primary peritoneal carcinoma

The peritoneum is a serous lining of mesothelial cells with rich vascular and lymphatic capillary network that covers the abdominal and pelvic walls and organs. Peritoneal neoplasia can originate de novo from the peritoneal tissues (primary) or invade or metastasize into the peritoneum from adjacent or remote organs (secondary).

Primary peritoneal carcinoma (ie, serous surface papillary carcinoma) arises primarily from peritoneal cells. The mesothelium of the peritoneum and the germinal epithelium of the ovary arise from the same embryologic origin; therefore, the peritoneum may retain the multipotentiality allowing the development of a primary carcinoma.

This rare malignancy predominantly affects postmenopausal women typically with multicentric peritoneal and omental involvement. It resembles papillary serous ovarian carcinoma in pathological and clinical aspects. This malignancy is differentiated from its ovarian counterpart by the fact that it involves the extraovarian peritoneum significantly and the ovarian surface minimally or not at all. Extensive calcification or omental caking is present in many cases and is a useful CT finding to exclude mesothelioma. The absence of an ovarian mass is critical for excluding metastatic papillary serous ovarian carcinoma, which otherwise has a similar CT appearance.

Treatment of this malignancy is very similar to that of epithelial ovarian cancer, which includes combination chemotherapy after optimal cytoreductive surgery. Doxil or topotecan would be appropriate second line treatments.

Sebbag G, Shmookler BM, Chang D, Sugarbaker PH. Peritoneal carcinomatosis from an unknown primary site. Management of 15 patients. Tumori. Mar-Apr 2001;87(2):67-73

Nam JH, Kim YM, Jung MH, Kim KR, Yoo HJ, Kim DY, et al. Primary peritoneal carcinoma: experience with cytoreductive surgery and combination chemotherapy. Int J Gynecol Cancer. Jan-Feb 2006;16(1):23-8

Cormio G, Di Vagno G, Di Gesu G, Mastroianni M, Melilli GA, Vimercati A, et al. Primary peritoneal carcinoma: a report of twelve cases and a review of the literature. Gynecol Obstet Invest. 2000;50(3):203-6.

Ca-125 for breast cancer

CA-125 is an important part of the workup for suspicious adnexal massess and for for following treated ovarian cancer. It is not a common marker in clinical use for breast cancer and  not much is known about it. In one recent study, thirty-three patients had increasing or continuously high concentrations of CA 125. Thirty (91%) of these had involvement of the pleura, either as pleural metastasis or metastasis in surrounding tissue i.e. bone structures in the thorax cavity or lung parenchyma. MUC1 and CEA were elevated in 27 (82%) and 24 (73%) of the 33 patients, respectively. Increased concentrations of these two markers did not relate to the site of metastasis. However, the three tumor markers complemented each other in detecting early metastases. Increased CA 125 was associated with metastasis in or near the pleura, and in stage IV breast cancer it was related to poor prognosis. Another study suggested that it can be elevated with any cancer that involves pleural surface, just like ovarian cancer involves peritoneal surface. As such, Ca-125 can be potentially misleading if used as marker for breast cancer.

Samuel S et al, .Validation of Referral Guidelines for Women With Pelvic Masses
Obstetrics & Gynecology 2005;105:35-41

Amy C. Dearking et al, How Relevant Are ACOG and SGO Guidelines for Referral of Adnexal Mass?Obstetrics & Gynecology 2007;110:841-848

Lars F. Noruma et al, Elevated CA 125 in Breast Cancer - A Sign of Advanced Disease Tumor Biology Vol. 22, No. 4, 2001   

D. Shitrit, B. Zingerman, A. B.-G. Shitrit, D. Shlomi, and M. R. Kramer
Diagnostic Value of CYFRA 21-1, CEA, CA 19-9, CA 15-3, and CA 125 Assays in Pleural Effusions: Analysis of 116 Cases and Review of the Literature
Oncologist, August 1, 2005; 10(7): 501 - 507.

Alimta (premetrexed) for ovarian cancer

Pemetrexed (Alimta) is an antifolate agent that possesses antitumor activity in a variety of solid tumors, including mesothelioma and non-small-cell lung, gastrointestinal, head and neck, breast, and gynecologic cancers.
The observation of responses in patients with ovarian cancer in phase I studies of the combination of pemetrexed and gemcitabine prompted the development of a phase II trial of the combination as secondline chemotherapy in patients with recurrent platinum-sensitive or -resistant ovarian primary cancers. The study regimen consists of gemcitabine at 1,000 mg/m2 on days 1 and 8 in combination with pemetrexed at 500 mg/m2 on day 8 every 21 days, with pemetrexed being given before gemcitabine on day 8. All patients are receiving folic acid and B12 supplementation and dexamethasone pretreatment. Among the first five evaluable patients accrued (four with platinum-sensitive disease), measurable disease response and decreased cancer antigen- 125 levels have been observed in four. Four of these patients are off study- three due to toxicity and one due to progressive disease; one patient has received at least four cycles of study treatment. To date, six patients are enrolled (five with platinum-sensitive disease, one platinum-resistant); no formal efficacy analysis has been conducted. There may be a particularly strong rationale for use of pemetrexed in the setting of ovarian cancer. Folate receptor- alpha is a marker for ovarian cancer found in approximately 70% of ovarian tumors, and expression of the receptor is associated with poorer survival; the targeting of these receptors by folate enables 111INDTPA folate to be used to image ovarian tumors. There is evidence that pemetrexed targets these receptors, suggesting the potential for preferential activity of the drug in ovarian tumor cells.
Ely Lily recently released toxicity results of its study of Alimta for ovarian cancer, 9710, A Randomized, Double-Blind, Phase 2 Study of Two Doses of Pemetrexed in the Treatment of Platinum-Resistant, Epithelial Ovarian or Primary Peritoneal Cancer. So far that the two arms look the same in terms of response rates.

http://www.clinicalstudyresults.org/documents/company-study_3496_0.pdf

Campbell IG, Jones TA, Foulkes WD, et al: Folate-binding protein is a marker for ovarian cancer. Cancer Res 51:5329-5338, 1991.

Toffoli G, Russo A, Gallo A, et al: Expression of folate binding protein as a prognostic factor for response to platinum-containing chemotherapy and survival in human ovarian cancer. Int J Cancer 79:121-126, 1998.

Siegel BA, Dehdashti F, Mutch DG, et al: Evaluation of 111In-DTPA-folate as a receptor- targeted diagnostic agent for ovarian cancer: Initial clinical results. J Nucl Med 44:700-707, 2003.

Uterine fibroid embolization (UFE)

Lay Summary: Uterine fibroid embolization (UFE) is a minimally invasive treatment for fibroid tumors in the uterus. It is appropraite in properly selected patients.

Fibroid tumors, also known as myomas, are masses of fiber and muscle tissue in the wall of the uterus. Although these tumors are not cancerous, they may cause heavy menstrual bleeding, pain in the pelvic region and pressure on the bladder or bowel.

In a uterine fibroid embolization procedure, physicians use image guidance to place a synthetic material called an embolic agent inside one or more of the blood vessels that supply the fibroid tumors with blood. As a result, these vessels become occluded, or closed off, and the fibroid tissue shrinks. In most cases, symptoms are relievedAt this time, the Task Force recommends that uterine artery embolization (UAE) be offered to only patients with symptomatic uterine leiomyomata. Because the symptoms associated with leiomyomata can also be caused by other processes, it is critical that patients undergo preprocedural evaluation that is adequate to confirm that their symptoms are in fact caused by leiomyomata or significantly contributed to by leiomyomata. It is equally critical that unrelated but potentially more important processes (such as ovarian malignancy) be excluded.

Andrews RT, Spies JB, Sacks D, Worthington-Kirsch RL, Niedzwiecki GA, Marx MV, Hovsepian DM, Miller DL, Siskin GP, Raabe RD, Goodwin SC, Min RJ, Bonn J, Cardella JF, Patel NH. Patient care and uterine artery embolization for leiomyomata. J Vasc Interv Radiol 2004 Feb;15(2 Pt 1):115-20. PubMed

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Adjuvant chemo for stage 1b breast cancer

Mammographic screening has led to an increase in the number of small, node-negative breast cancers being diagnosed. Node-negative breast cancers that are  1 cm are stage T1a,bN0M0. Controversy surrounds the prognosis of these patients with locoregional therapy only and the need for adjuvant systemic therapy.

Early studies reported 10-year relapse-free survival (RFS) rates higher than 90% without adjuvant systemic therapy, but some more recent data suggest inferior outcomes. High tumor grade is the most consistent factor associated with poor prognosis. Other adverse prognostic factors are younger age, lymphovascular invasion (LVI), high Ki-67, and larger tumors within the T1a,b subgroup. Patients with high-grade tumors and/or LVI may have 10-year RFS rates of less than 75% in the absence of systemic therapy. The prognostic significance of hormone receptor status is unclear. Current guidelines for the systemic management of early-stage breast cancer differ when applied to stage T1a,bN0M0, reflecting the controversial nature of the issue.

Whether Oncotype can provide a relaible method of making treatment decisions in these pateitns is not known. A phase III trial, Tailorx, is being conducted to answer this question.

O. Hanrahan, A. M. Gonzalez-Angulo, S. H. Giordano, R. Rouzier, K. R. Broglio, G. N. Hortobagyi, and V. Valero
Overall Survival and Cause-Specific Mortality of Patients With Stage T1a,bN0M0 Breast Carcinoma
J. Clin. Oncol., November 1, 2007; 25(31): 4952 - 4960.

Emer O. Hanrahan, Vicente Valero, Ana M. Gonzalez-Angulo, Gabriel N. Hortobagyi
Prognosis and Management of Patients With Node-Negative Invasive Breast Carcinoma That Is 1 cm or Smaller in Size (stage 1; T1a,bN0M0): A Review of the Literature Journal of Clinical Oncology, Vol 24, No 13 (May 1), 2006: pp. 2113-2122

L Mauriac, A Keshaviah, M Debled, H Mouridsen, J. Forbes, B Thurlimann, R Paridaens, A Monnier, I Lang, A Wardley, et al.
Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial
Ann. Onc., May 1, 2007; 18(5): 859 - 867.

Taxotere Adriamycin Cytoxan for adjuvant therapy of breast cancer

Since 1998, the standard of care for patients with node-positive breast cancer in the United States and other parts of the world has been treatment with doxorubicin and cyclophosphamide followed by the taxane paclitaxel. Herceptin is added for HER+ disease.  This treatment regimen was based on an intergroup study demonstrating that the addition of paclitaxel to doxorubicin and cyclophosphamide (AC) led to rates of disease-free survival of 70 percent and overall survival of 80 percent at five years, as compared with 65 percent and 77 percent, respectively, for doxorubicin and cyclophosphamide alone, with modest differences in the rate of toxic effects. The next step was the development of the TAC regimen, in which a taxane is given concurrently with AC.

TAC is clearly effective in node positive women. Adjuvant chemotherapy with docetaxel reduced the risk of death from node-positive early-stage breast cancer by 30% at 55 months of follow-up in a major phase III trial. The combination of docetaxel (Taxotere), doxorubicin (Adriamycin), and cyclophosphomide (Cytoxan) (TAC) also cut the risk of relapse by 28% compared with the standard three-drug regimen of 5-fluorouracil, doxorubicin, and cyclophosphomide (FAC).

The Breast Cancer International Research Group (BCIRG) conducted the trial known as BCIRG 001. The randomized study enrolled 1,491 women in 20 countries from June 1997 to June 1999. The new data are based on 55-month follow-up from 92% of participants. Disease-free survival reached 75% for the women receiving TAC vs. 68% for those receiving FAC. This translated into a hazard ratio of 0.72 (P = .0010). Overall survival at five years was 81% for the FAC cohort compared with 87% for the women receiving TAC (hazard ratio, 0.70; P = .0080). Subgroup analyses showed relapse rates decreased 27% in estrogen receptor–positive women and 34% in those who were estrogen receptor–negative. While women with one to three nodes fared better than those with four or more, both benefited; the hazard ratios were 0.61 (P = .0009) for the former and 0.82 (P = .1629) for the latter.
Patients with HER2-neu amplification also did better on TAC. The hazard ratio for HER2-positive patients receiving TAC was 0.61 (P = .0118) and for HER2-negative patients it was 0.76 (P = .0380). The only group that did not show significantly better outcomes on TAC compared to FAC was women with four or more positive lymph nodes. Among these participants, there was a trend toward superior results with TAC vs. FAC, but it did not reach statistical significance.

The absolute benefit in patients with node-negative disease may be much smaller and this may not outweigh the expected increase in toxicity. Martin et al. reported on the results of a randomized adjuvant trial comparing TAC with FAC for high-risk N0 breast cancer patients, the GEICAM 9805 trial. Comparisons are reported for toxicity and quality of life, not for efficacy, as follow-up time is still too short. After a protocol amendment, patients on the TAC arm received primary granulocyte colony-stimulating factor (G-CSF) prophylaxis, whereas before the amendment, only secondary G-CSF prophylaxis was allowed or even mandatory after an episode of febrile neutropenia. Unfortunately the report centered only on toxicity and we are still awaiting publication of this important study.

For node negative women, guidelines recommend: For premenopausal women at average to high risk, but whose tumors are hormonally responsive, ovarian ablation and tamoxifen, chemotherapy and tamoxifen, tamoxifen alone, or ovarian ablation alone can be considered standard therapy. Node-negative and premenopausal women with hormone-unresponsive cancer should be offered chemotherapy with AC, CMF, or cyclophosphamide-adriamycin-fluorouracil (CAF).

Other guidelines, however, NCCN, for exampel, are not as stringent on assigning specific regimens to either node+ or node negative group.

Ahluwalia M. S., Daw H. A., Noronha V., Martin M., Vogel C., the Breast Cancer International Research Group Adjuvant Docetaxel for Node-Positive Breast Cancer.

N Engl J Med 2005; 353:954-955, Sep 1, 2005

Breast Cancer Disease Site Group. Adjuvant systemic therapy for node-negative breast cancer [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2003 May 1 [online update]. 22 p. (Practice guideline report; no. 1-8). [79 references]

nccn.org, breast cancer

Martin M, Lluch A, Segui M et al. Toxicity and health-related quality of life in breast cancer patients receiving adjuvant docetaxel, doxorubicin, cyclophosphamide (TAC) or 5-fluorouracil, doxorubicin and cyclophosphamide (FAC): impact of adding primary prophylactic granulocyte-colony stimulating factor to the TAC regimen. Ann Oncol 2006; 17: 1205–1212.

Leupron ro Zoladex for ovarian function preservation on chemotherapy

The luteinising hormone-releasing hormone analogue goserelin (‘Zoladex’) suppresses ovarian oestrogen production in pre- and perimenopausal women. Goserelin is a biodegradable, sustained-release 3.6 mg depot that is administered by subcutaneous injection every 28 days. Clinical trials in premenopausal women with hormone-sensitive early breast cancer have demonstrated that goserelin alone, or in combination with tamoxifen, is at least as effective as cyclophosphamide, methotrexate, 5-fluorouracil (CMF) chemotherapy.

Ovarian failure and infertility following adjuvant chemotherapy for early breast cancer are major concerns for some young women. Techniques for oocyte harvesting are associated with delay in starting treatment, potentially undesirable estrogen stimulation and a relatively low success rate. We report an audit of our experience with the luteinising hormone-releasing hormone agonist, goserelin, to achieve transient ovarian suppression during chemotherapy as a means of preserving ovarian function. The American Society of Clinical Oncology's recommendations on fertility preservation in cancer patients (Lee, et al., 2006) stated that sperm and embryo cryopreservation are considered standard practice. On the other hand, the use of GNRH analogs or antagonists for testicular or ovarian suppression is considered investigational. ASCO guidelines state: “At this time, since there is insufficient evidence regarding the safety and effectiveness of GnRH analogs and other means of ovarian suppression on female fertility preservation, women interested in ovarian suppression for this purpose are encouraged to participate in clinical trials.” The guidelines also noted that there is insufficient evidence of the effectiveness of GnRH analogues in preventing chemotherapy-induced gonadal damage in men: “The efficacy of gonadoprotection through hormonal manipulations has only been evaluated in very small studies in cancer patients.”

In a review of the literature, Sonmezer and Oktay (2006) explained that there are a limited number of prospective studies of GNRH analogues in preventing chemotherapy-induced gonadal damage, “which are flawed because of short-term follow-up and/or because of lack of control subjects.” The review notes that “[i]n addition to the lack of consistent support from clinical studies, there is currently no biological explanation for who GNRHa [GNRH analogues] can affect ovarian reserve.” The authors concluded that “[i]n the absence of a prospective randomized study with sufficient power, we do not rely on ovarian suppression as an effective means of fertility preservation.”

Ander Urruticoechea et al, Ovarian protection with goserelin during adjuvant chemotherapy for pre-menopausal women with early breast cancer (EBC) Journal Breast Cancer Research and Treatment Published online: 13 September 2007 http://www.springerlink.com/content/bg74271g146x8511/

Lee SJ, Schover LR, Partridge AH, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol. 2006;24(18):2917-2931.

Sonmezer M, Oktay K. Fertility preservation in young women undergoing breast cancer therapy. Oncologist. 2006;11(5):422-434.

Taxotere for ovarian cancer

Lay Summary: Taxotere is essentially as effective as Taxol in ovarian cancer.

The combination of paclitaxel and Paraplatin® is the most common chemotherapy regimen for the initial treatment of patients with advanced or metastatic ovarian cancer. The limiting toxicity of this drug combination is neurotoxicity. Although the combination of paclitaxel and Paraplatin® is associated with a high response rate, the majority of women with stage III and IV ovarian cancer ultimately relapse and will need salvage chemotherapy. There is in-vitro evidence to suggest that Taxotere® and paclitaxel are not completely cross resistant and clinical responses to Taxotere® have been observed in patients who have failed Paraplatin® and paclitaxel. The response rate of patients with ovarian cancer who have failed Paraplatin® and paclitaxel and were treated with Taxotere® has been determined in a Gynecologic Oncology Group (GOG) clinical trial. The results of this clinical trial were published in the February 2003 issue of Gynecologic Oncology. 1

This study involved 60 patients who had disease progression within 6 months of receiving a platinum and paclitaxel-based regimen. Taxotere® was administered at a dose of 100 mg/m2 every 21 days. The response rate was 22.4%, with 5.2% being complete and a median duration of response of 2.5 months. The major dose-limiting toxicity was neutropenia which led to dose reductions in 36% of patients. There was one treatment-related death. Neurotoxicity did not appear to be a major problem. These authors concluded that “Taxotere® is active in paclitaxel-resistant ovarian and peritoneal cancer but, in view of significant hematologic toxicity, further study is warranted to ascertain its optimal dose and schedule”.

This study is of interest as it confirms previous reports of responses to Taxotere® after failure of paclitaxel-containing regimens. However, the response rates were low and the duration of responses short. There is, however, emerging evidence to suggest that Taxotere® may be a better drug for the initial treatment of ovarian cancer than paclitaxel.

The status of Taxotere® for the treatment of ovarian cancer has been the subject of a recent review by Drs Kaye and Vasey. 2 In this review, they summarized the outcome of a large clinical trial carried out in England and Europe. A total 1,077 newly diagnosed patients with stage Ic-IV ovarian cancer were randomly allocated to be treated with Paraplatin® and Taxotere® or Paraplatin® and paclitaxel. They reported that “Patients treated with paclitaxel plus carboplatin experienced significantly greater neurotoxicity than those treated with docetaxel plus carboplatin. Docetaxel/carboplatin and paclitaxel/carboplatin produced similar rates of objective response (66% and 62%, respectively), and initial data on progression-free survival indicate that the two treatments appear very similar in efficacy”. This study strongly suggests that Taxotere® may be the best drug to combine with Paraplatin® for the initial treatment of ovarian cancer.

1. Rose P, Blessing J, Boll H, et al. A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal cancer: A Gynecologic Oncology Study Group study. Gynecologic Oncology. 2003;88:130-135.

2. Kaye S, Vasey P. Docetaxel in ovarian cancer: phase III perspectives and future development. Seminars in Oncology. 2002;29(3 Suppl 12):22-7.

Taxotere and Gemcitabine for metastatic breast cancer

Lay Summary: I discuss the Taxotere and Gemzar combination.

Taxotere and gemcitabine in combination have been tested in phase II. Results from the first study,  39-patient, phase II clinical trial showed a response rate of 79 percent, with two complete responses and 29 partial responses. Twenty-five of these patients remained responsive for more than six months.
The median survival for the entire study population is 24.5 months, with no significant difference between the 30 patients who received prior chemotherapy in the adjuvant setting only, and the nine patients with prior chemotherapy for metastatic disease. The one-year survival is 74 percent for the entire study population, and the two-year survival is estimated to be 53 percent.

There have now been 6 studies. In phase II trials using every-2-week regimens of gemcitabine at 1,500 or 2,000 mg/m2 on day 1 and docetaxel at 50 or 65 mg/m2 on day 1 or 55 mg/m2 on day 8, response rates were 50% in pretreated patients and 66% in treatment-naive patients.

In a recent phase III trial reported by O'Shaughnessy et al 511 anthracycline- pretreated patients with metastatic breast cancer received oral capecitabine at 1,250 mg/m2 twice daily for 14 days plus docetaxel at 75 mg/m2 on day 1 every 3 weeks or docetaxel alone at100 mg/m2 every 3 weeks. The capecitabine/docetaxel doublet was associated with a significantly higher objective response rate (42% vs 30%) and significant improvements in median overall survival (14.5 vs 11.5 months) and 1-year survival rates (57% vs 47%). Analyses of delivered treatment indicated that early in the trial, capecitabine doses were reduced to approximately 1,000 mg/m2 twice daily due to poor tolerability (diarrhea and hand-foot syndrome) and were maintained at that level throughout treatment. These results suggest that the capecitabine/ docetaxel and not Taxotere alone should be considered a standard of treatment in the setting of metastatic breast cancer.  Whether gemcitabine is better with Taxotere is better than Xeloda and taxotere is unknown.

guidance.nice.org.uk/TA116

National Institute for Health and Clinical Excellence (NICE). Gemcitabine for the treatment of metastatic breast cancer. London (UK): National Institute for Health and Clinical Excellence (NICE); 2007 Jan. 24 p. (Technology appraisal guidance; no. 116).

Dent S, Messersmith H, Trudeau M, Breast Cancer Disease Site Group. The role of gemcitabine in the management of metastatic breast cancer: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2007 Jan 22. 5 p. (Evidence-based series; no. 1-12). [11 references]

Lenz F, Beldermann F, Geberth M, et al. A phase II study of first-line combination chemotherapy with docetaxel and gemcitabine in anthracycline-pretreated, Her-2 negative metastatic breast cancer. Proceedings from the 12th European Conference on Clinical Oncology. Sept. 21-25, 2003. Copenhagen, Denmark.

ANDREW D. SEIDMAN,  Gemcitabine and Docetaxel in Metastatic Breast Cancer ONCOLOGY December 2004 • Volume 18 Number 14 Supplement 12