ONCOLOGY Vol 19 No 6

Squamous cell carcinomas of the head and neck are highly responsiveto induction chemotherapy. However, randomized trials have failedto demonstrate a survival advantage with the addition of induction chemotherapyto locoregional therapy consisting of surgery and/or radiationtherapy. Currently, concomitant radiation and chemotherapy hasemerged as a standard and has optimized locoregional control in headand neck cancer. In this setting, the addition of induction chemotherapymay further improve outcome by enhancing both locoregional and distantcontrol. As interest in induction regimens is renewed, we elected toconduct a systematic review of trials of induction chemotherapy forlocoregionally advanced head and neck cancer. The most studied combination-cisplatin plus fluorouracil (5-FU)-achieves objective responserates of about 80%. In a meta-analysis, induction with platinum/5-FU resulted in a small survival advantage over locoregionaltherapy alone. The introduction of a taxane into induction chemotherapyregimens has produced promising results. Induction chemotherapyshould be the subject of further clinical research in head andneck cancer. Randomized clinical trials in which the control arm isconcurrent chemoradiotherapy and the experimental arm is inductionchemotherapy followed by concurrent chemoradiotherapy are planned.Platinum/taxane combinations are the preferred regimens for furtherstudy in the induction setting and a suitable platform with which toinvestigate the addition of novel targeted agents.

The manuscript by Jubran et albrings to light the many controversiessurrounding the managementof intracranial germ cell tumors.Perhaps the most controversialissues are the roles of radiotherapyand chemotherapy in the treatment ofpure germinoma and nongerminomatousgerm cell tumor (NGGCT).

Drs. Partridge and Schapira areto be complimented on a conciseand comprehensive reviewof pregnancy before, during, andafter a diagnosis of breast cancer. Aswomen are able and willing to deferpregnancy until later in life, the issuesaddressed in this article will be encounteredwith increasing frequencyin oncology.

Drs. Patridge and Schapira setout to review breast cancerand pregnancy, discuss treatmentoptions for breast cancer duringpregnancy, and summarize the availableevidence regarding safety of pregnancyafter breast cancer. This is asubstantial undertaking. They beginby reviewing the epidemiologic dataindicating an early increase in risk ofbreast cancer development after pregnancyand the likely long-term protectiveeffect of pregnancy on breastcancer risks. The subsequent focus oftheir review is on breast cancer duringpregnancy, a relatively rare occurrence.In a study from California,Smith et al indicated that the frequencyof breast cancer concurrent withpregnancy was 1.3 per 10,000 livesingleton births.[1] The authors notea frequently quoted figure of 1 in 3,000pregnancies.

The variability and complexity of central nervous system germ cell tumors have led to controversy in both diagnosis and management. If a germ cell tumor is suspected, the measurement of cerebrospinal fluid and serum alpha-fetoprotein and beta–human chorionic gonadotropin is essential. A histologic specimen is not necessary if the patient has elevated levels; however, if the tumor markers are negative, a biopsy is needed to confirm the diagnosis of a germinoma. Germinomas are extremelyradiosensitive, enabling 5-year survival rates that exceed 90%. Treatment has traditionally included focal and craniospinal axis irradiation; however, multiple ongoing studies are being conducted to examinethe efficacy of reduction or elimination of radiation therapy with the addition of chemotherapy. Nongerminomatous germ cell tumors, on the other hand, are relatively radioresistant with a poorer outcome. The combination of chemotherapy and irradiation is associated with overall survival rates of up to 60%. This article provides a review of the controversies in diagnosis and treatment of central nervous system germ cell tumors.

Drs. Jubran and Finlay havewritten a timely review thatarticulates the trials and tribulationsof treating central nervous system(CNS) germ cell tumors. Theirreview comes on the heels of the Children’sOncology Group (COG) nongerminomatousgerm cell tumor study(ACNS0122) that opened January 26,2004, and in anticipation of the COGgerminoma study (ACNS0232) thatmay open in 2005.

Increasing epidemiologic data haveemerged to support an associationbetween 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductaseinhibitor (statin) use and theprevention or delay in the developmentof invasive cancer. The inhibitionof HMG-CoA reductase resultsin the depletion of mevalonate, a precursorof cholesterol, but also of geranylgeranylpyrophosphate andfarnesyl pyrophosphate, both ofwhich are critical for the isoprenylationof important cellular signalingproteins. Alterations in function andexpression of these signaling proteins-particularly Ras and Rho-have been implicated in malignanttransformation and proliferation. Furthermore,the epidemiologic data arebeing surpassed by preclinical datasupporting the concept that inhibitionof critical signaling pathways bystatins can lead to increased cell deathand prevent the proliferation of malignantcells.

Statins inhibit the activity of the rate-limiting enzyme in the cholesterolbiosynthetic pathway, HMG-CoA reductase, and are widely prescribedfor lowering plasma lipid levels. Several statins have antitumor effects inexperimental models, and observational studies suggest that this anticanceractivity in the laboratory may translate into effective treatments and/orpreventive strategies for certain human cancers. This paper reviews thelaboratory and clinical evidence that statins have anticancer activity, discussesthe possible mechanisms by which tumor growth may be inhibitedby this class of drugs, and outlines strategies for the evaluation of theseagents in the prevention and treatment of human cancers.

The relationship between pregnancy and breast cancer is complex,and a paucity of available data further complicates decision-makingfor many women diagnosed with breast cancer during pregnancy ordesiring to become pregnant after such a diagnosis. Treatment of breastcancer during pregnancy requires a multidisciplinary care team andcareful consideration of the risk of the disease and gestational age ofthe fetus, in conjunction with the patient’s preferences. Chemotherapyshould be deferred beyond the first trimester. There is no evidence thatpregnancy in a breast cancer survivor will decrease long-term survival;in fact, studies suggest a potential protective effect of pregnancy afterbreast cancer in terms of the risk of recurrence. However, the availablestudies are limited by substantial potential biases, and concerns remainfor some women and their doctors about the risks of pregnancy afterbreast cancer. This article reviews what is known about the associationbetween pregnancy and breast cancer, discusses treatment options forwomen diagnosed with the disease during pregnancy, and summarizesevidence regarding the safety of pregnancy after breast cancer.