Cancer Treatment Today » Chemotherapy

Weekly Taxol for breast cancer – pro

M Levin, MD — Fri, 08 Feb 2013 20:04:36 +0000

Weekly paclitaxel is FDA approved; or, at least, the FDA indication does not exclude the weekly schedule. TAXOL is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.

There are now several studies that confirm that it is of similar effectiveness to every three week single agent pacltaxel but less toxic. In the adjuvant setting, a randomized clinical trial showed that weekly doses of the drug paclitaxel (Taxol®) following surgery and standard chemotherapy improves disease-free and overall survival in women with breast cancer. For metastatic disease, NCCN lists both the three weekly and once weekly regimens on p. BINV-O, 2.

There are many studies of weekly Taxol in combination with other drugs.

Burris H 3rd, Yardley D, Jones S, et al. Phase II trial of trastuzumab followed by weekly paclitaxel/carboplatin as first-line treatment of patients with metastatic breast cancer. J Clin Oncol 2004;22:1621–1629.

Sparano JA, Wang M, Martino S, Jones V, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. New England Journal of Medicine. 2008 Apr 17;358(16);1663-1671.

I. Abdel Halim, M. El Ashri, W. El Sadda, Weekly paclitaxel versus standard 3-week schedule in patients with metastatic breast cancer. J Clin Oncol 29: 2011 (suppl; abstr 627)

JUN HORIGUCHI1, YOSHIAKI RAI2, KAZUO TAMURA3, TOSHIHIKO TAKI4, KAZUFUMI HISAMATSU Phase II Study of Weekly Paclitaxel for Advanced or Metastatic Breast Cancer in Japan, Anticancer Research February 2009 vol. 29 no. 2 625-630

For Lay version see here

Taxotere and Cytoxan for metastatic breast cancer – pro

M Levin, MD — Thu, 18 Oct 2012 02:41:24 +0000

Preclinical data demonstrate in vitro synergy for combinations of docetaxel (Taxotere) and cyclophosphamide. As single agents, both drugs have proven highly active against breast cancer, and the activity of the combination has been confirmed by several phase II studies. More recently, it has proven adjuvant efficacy on par with anthracycline containing regimen in a trial to directly compare AC to Taxotere/Cytoxan (TC) as adjuvant treatment in breast cancer. This recent trial showed that TC improves disease-free survival compared with AC for the treatment of adjuvant breast cancer. Although cardiac side effects were not presented, the researcher noted that TC does not appear to have the cardiotoxicity issues associated with AC, which is a very important issue for some patients. NCCN considers TC an appropriate regimen for adjuvant treatment for breast cancer. and NCCN 2012 lists this regimen on p. BINV-K.However, NCCN does not list it for metastatic disease.

MB Whitmore, JA Waddell, DA Solimando, JrCancer Chemotherapy Update-Docetaxel and Cyclophosphamide Regimen in the Treatment of Breast Cancer, Hospital Pharmacy, 2008

nccn, 2012, BINV-O

Dennis Slamon, M.D., Ph.D., Wolfgang Eiermann, M.D., Nicholas Robert, M.D., Tadeusz Pienkowski, M.D., Miguel Martin, M.D., Michael Press, M.D., Ph.D., John Mackey, M.D., John Glaspy, M.D., Arlene Chan, M.D., Marek Pawlicki, M.D., Tamas Pinter, M.D., Vicente Valero, M.D., Mei-Ching Liu, M.D., Guido Sauter, M.D., Gunter von Minckwitz, M.D., Frances Visco, J.D., Valerie Bee, M.Sc., Marc Buyse, Sc.D., Belguendouz Bendahmane, M.D., Isabelle Tabah-Fisch, M.D., Mary-Ann Lindsay, Pharm.D., Alessandro Riva, M.D., and John Crown, M.D. for the Breast Cancer International Research Group Adjuvant Trastuzumab in HER2-Positive Breast Cancer N Engl J Med 2011; 365:1273-1283 October 6, 2011

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MUGA before and during chemotherapy – pro

M Levin, MD — Tue, 04 Sep 2012 03:02:18 +0000

The MUGA scan (MUltiple Gated Acquisition scan) is a noninvasive tool for assessing the function of the heart. The MUGA scan produces a moving image of the beating heart, and from this image several important features can be determined about the health of the cardiac ventricles (the heart’s major pumping chambers) and a measurement of cardiac ejection fraction. The latter can be monitored during chemotherapy to diagnos cardiotoxicity and adjust chemo, is it is noted.

Guidelines recommend routine use of MUGA before the administration of doxorubicin for adjuvant therapy for breast cancer but this has recently been questioned. Nevertheless, serial MUGA scans are widely recommended and are standard of care at this time.

Sabel, Michael S.; Levine, Ellis G.; Hurd, Thelma; Schwartz, Gary N.; Zielinski, Robert; Hohn, David; Edge, Stephen B.Cancer Management Controversy
Is MUGA Scan Necessary in Patients With Low-Risk Breast Cancer Before Doxorubicin-Based Adjuvant Therapy?American Journal of Clinical Oncology: Cancer Clinical Trials:
August 2001 – Volume 24 – Issue 4 – pp 425-428

Keefe DL. Trastuzumab-associated cardiotoxicity. Cancer. 2002;95:1592-1600.

Breast Cancer: Prognosis, Treatment, and Prevention [ILLUSTRATED] (Hardcover)
by Jorge R. Pasqualini (Editor)
Informa Healthcare; 1 edition (July 17, 2002)
ISBN-13: 978-0824707125

Tykerb and Taxol for metastatic breast cancer – pro

M Levin, MD — Mon, 03 Sep 2012 23:11:06 +0000

The Taxol and Tykerb combination has recently been shown to improve quality of life in metastatic breast cancer patients versus Taxol alone. In a phase 3 randomized, multicenter, double-blind, placebo-controlled study, first-line therapy with lapatinib plus paclitaxel significantly improved clinical outcomes based on a pre-planned analysis of ErbB2+ metastatic breast cancer patients. The combination of investigational Tykerb (lapatinib) and Taxol (paclitaxel) as neoadjuant chemotherapy appears effective against inflammatory breast cancer, according to another small study. There are, as of yet in 2012, no published Phase III studies on survival for this regimen.

NCCN does not list the Taxol/Tykerb regimen.

Sherrill B, Di Leo A, Amonkar MM, Wu Y, Zvirbule Z, Aziz Z, Bines J, Gomez HL
Quality-of-life and quality-adjusted survival (Q-TWiST) in patients receiving lapatinib in combination with paclitaxel as first-line treatment for metastatic breast cancer. 2010-04, Curr Med Res Opin., 26(4):767-75.

Cristofanilli M, et al “A phase II combination study of lapatinib (TYKERB) and paclitaxel as neoadjuvant therapy in patients with newly diagnosed inflammatory breast cancer (IBC)” SABCS 2006; General Session 1: Abstract 1.

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Adjuvant chemo for stage 1b breast cancer – pro

M Levin, MD — Mon, 27 Aug 2012 17:34:26 +0000

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 patients 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.

Chemo for Choriocarcinoma – pro

M Levin, MD — Thu, 23 Aug 2012 21:04:30 +0000

Gestational trophoblastic disease comprises a spectrum of interrelated conditions originating from the placenta and includes the most agressive type, choriocarcinoma. Histologically distinct disease entities encompassed by this general terminology include complete and partial hydatidiform moles, invasive moles, gestational choriocarcinomas, and placental site trophoblastic tumors. Before the advent of sensitive assays for human chorionic gonadotropin (hCG) and efficacious chemotherapy, the morbidity and mortality from gestational trophoblastic disease were substantial. In agressive high-risk cases, aggressive multiagent chemotherapy and individualized multimodality therapy is warranted . At present, treatment with single-agent methotrexate or actinomycin D is recommended for low-risk disease, while intense combination regimens including EMACO (etoposide, methotrexate, actinomycin D, cyclosphosphamide and oncovin) are recommended for intermediate or high-risk disease. A recent guideline says this about the choice of chemotherapy: “•Women with high-risk metastatic disease should be treated with multiagent chemotherapy. This includes triple therapy with methotrexate, dactinomycin, and either chlorambucil or cyclophosphamide. More recent regimens further incorporate etoposide with or without cisplatin into combination chemotherapy.”.

Royal College of Obstetricians and Gynaecologists (RCOG). The management of gestational trophoblastic neoplasia. London (UK): Royal College of Obstetricians and Gyneacologists (RCOG); 2004 Feb. 7 p. (Guideline; no. 38). [16 references]

American College of Obstetricians and Gynecologists (ACOG). Diagnosis and treatment of gestational trophoblastic disease. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2004 Jun. 13 p. (ACOG practice bulletin; no. 53). [49 references]

Kufe D (2000). Benedict RC, Holland JF. ed. Cancer medicine (5th ed. ed.). Hamilton, Ont: B.C. Decker. ISBN 1-55009-113-1.

^Rustin GJ, Newlands ES, Begent RH, Dent J, Bagshawe KD (1989). “Weekly alternating etoposide, methotrexate, and actinomycin/vincristine and cyclophosphamide chemotherapy for the treatment of CNS metastases of choriocarcinoma”. J. Clin. Oncol. 7 (7): 900–3.

Herceptin and Gemcitabine for Breast Cancer – pro

M Levin, MD — Thu, 09 Aug 2012 18:17:02 +0000

Since a study demonstrated that Herceptin(trastuzumab) plus a taxane is associated with a clinical benefit that is superior to that of a taxane alone, a number of combinations have been studied, including Herceptin with gemcitabine. A 2006 review in “The Oncologist” cites two trials of gemcitabine/trastuzumab as a second-line therapy; in one trial this combination treatment resulted in a response rate of 36 percent, in the other trial a response rate of 38 percent. A 2009 study in “Clinical Breast Cancer” concluded that gemcitabine/trastuzumab, while effective, appeared to be less effective than trastuzumab in combination with vinorelbine or the taxanes, paclitaxel and docetaxel, which are other drugs commonly used to treat breast cancer. Another study, published in 2008 in “Cancer Chemotherapy Pharmacology,” evaluated gemcitabine/trastuzumab as a “salvage therapy” and found it “safe and potentially effective.”

Christian Jackisch HER-2-Positive Metastatic Breast Cancer: Optimizing Trastuzumab-Based Therapy The Oncologist September 2006 vol. 11 Supplement 1 34-41

De Mattos-Arruda, et al. Advances in First-Line Treatment for Patients with HER-2+ Metastatic Breast Cancer The Oncologist 2012; 17:631-644

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Dose dense adjuvant chemotherapy in breast cancer – pro

M Levin, MD — Wed, 20 Jun 2012 20:27:03 +0000

Since 1998, the standard of adjuvant 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. This regimen was first administered on a schedule of once every three weeks and then, more recently, once every two weeks, after a comparative trial demonstrated improved efficacy (a 7 percent absolute improvement in disease-free survival and a 2 percent improvement in overall survival at three years) with the schedule involving more frequent administration (referred to as dose-dense therapy).

The issues of toxicity are well worked out in both adjuvant and metastatic setting. In metastatic setting, dose dense chemo yilds higher response rates. Weekly administration of the drug paclitaxel (Taxol®) to patients with breast cancer that had spread to other parts of the body resulted in a higher response rate and a longer delay until patients’ disease progressed, compared with conventional administration of the drug every three weeks. A Phase III trial conducted in Germany studied 1284 patients under the age of 65 who had at least four lymph nodes containing metastatic cancer. Patients were assigned to receive either dose-dense chemotherapy or conventional treatment. At five years the relapse-free survival was 70 percent in the dose-dense arm, compared with 62 percent in the conventional-dose arm. Patients did seem to have a lower quality of life with the dose-dense method of treatment but recovered after a few months.

In terms of effectiveness, there is only one study, as cited above. NCCN lists dose-dense therapy. Although this one study has given promising results, it’s still too early to say if dose-dense chemotherapy is better than standard chemotherapy. However, there is expert consensus that it is not worse and not more toxic. It is thus equivalent to q 3 weeks non-dense therapy and should not be considered experimental or not med. necessary. The drugs themselves are FDA approved: “TAXOL is indicated for the adjuvant treatment of node-positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy.”

Citron ML et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First report of Intergroup trial C9741/Cancer and Leukemia Group B trial 9741. J Clin Oncol 2003;21(7):1-9.

Jackisch C, Von Minckwitz G, Raab G, et al. Primary endpoint analysis of the GEPARDUO study — preoperative chemotherapy comparing dose-dense versus sequential Adriamycin/docetaxel combination in operable breast cancer. Program and abstracts of the 25th Annual San Antonio Breast Cancer Symposium; December 11-14, 2002; San Antonio, Texas. Abstract 152.

Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C.Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840.J Clin Oncol. 2008 Apr 1;26(10):1642-9. Comment in: J Clin Oncol. 2008 Apr 1;26(10):1585-7.

nccn, breast cancer, BINVK-7, 2017

H. Joensuu et al, Adjuvant treatments for triple-negative breast cancers Ann Oncol (2012) 23 (suppl 6): vi40-vi45.

Taxol and Carboplatin for Neoadjuvant Therapy – pro

M Levin, MD — Tue, 19 Jun 2012 15:58:11 +0000

Two independent phase II studies have shown that the combination of carboplatin and docetaxel (Taxotere®; Aventis Pharmaceuticals, Inc.; Bridgewater, NJ) is active in the first-line treatment of metastatic breast cancer. Based on these promising results, nonanthracycline alternatives were investigated, with many of them incorporating platinum agents. A recent review concluded: “In several phase II studies, combination carboplatin and paclitaxel (Taxol®; Bristol-Myers Squibb) therapy was active and reasonably well tolerated in the first-line treatment of metastatic breast cancer, producing objective response rates of 53%–62%—substantially higher rates than those seen in other phase II trials of either drug alone. Similar phase II data for carboplatin with docetaxel (Taxotere®; Aventis; Bridgewater, NJ) have been reported, and recent phase III data suggest that adding carboplatin to a paclitaxel/trastuzumab regimen produces superior efficacy than paclitaxel/trastuzumab alone for patients with HER2+ metastatic disease. Drug scheduling plays an important role in the therapeutic ratio of this combination treatment.”

There is less information on using this regimen for neoadjuvant therapy. There are Phase II studies that suggest the weekly schedule for the neoadjuvant settings. NCCN does not specifically list this regimen for neaodjuvant use. However, on p. BINV-12 NCCS says: “in general, dose chemotherapy regimens recommended in the adjuvant setting may be considered in the preoperative setting”. Nevertheless, and NCCN does not recommend this regimen in the adjuvant setting either.

J. W. Chia, P. Ang, H. See, Z. Wong, L. Soh, Y. Yap, N. Wong Triple-negative metastatic/recurrent breast cancer: Treatment with paclitaxel/carboplatin combination chemotherapy. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 1086

X. S. Chen et al, Weekly paclitaxel plus carboplatin is an effective nonanthracycline-containing regimen as neoadjuvant chemotherapy for breast cancer Ann Oncol (2010)
doi: 10.1093/annonc/mdq041

nccn.org, BINV-12 and BINV-K, 2012

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