Recent Report on carcinoma larynx

Recent reports that show promise of practical clinical utility include the following:

The immortalizing enzyme, telomerase, has been linked to carcinogenesis and its confirmed presence in laryngeal
P.1728
cancer specimens may provide a novel molecular marker, especially for diagnosing persistent malignancy after radiation failure (1).
A form of hyaluronidase, PH-20, which is expressed in primary laryngeal cancer tissue, is elevated even more in metastatic lesions, such that it can serve as a useful tumor marker and have prognostic value (2).
Using polymerase chain reaction techniques, herpes simplex virus DNA was found in 75% of laryngeal cancers, but only in 25% of oral cancers and in no control biopsy tissue, suggesting that it may be a cocarcinogen in some patients (3).
Mutations of the p53 gene have been found to correlate with the clinical outcome of patients with laryngeal cancer. The predictive power of p53 gene mutations is an area of high research interest at this time (4).
Retinoblastoma protein expression negativity is associated with a higher likelihood of lymph node metastasis and a significantly lower 5-year survival rate (5).
Low levels of cyclin D1 can be detected by immunohistochemical staining of paraffin-embedded specimens.
Low levels of cyclin D1 correlate with radio-resistant early-stage larynx carcinoma (6).



Technorati Tags: telomerase, hyaluronidase

Radiotherapy for Early Glottic Cancer

The optimal clinical scenario for using XRT in early glottic cancer is diffuse superficial disease (T1b, T2b) in which surgical intervention would disrupt the basic architecture of both vocal folds, the anterior commissure tendon, or the laminae propria.
The disadvantages of XRT include treatment of noncancerous vocal-fold tissue (T1a, T2a), which frequently results in scarring of the mucosa of the normal vocal fold with associated dysphonia (13).
DIAGNOSIS STAGING

• Laryngeal examination and videostroboscopy
• Panendoscopy with biopsy and mapping of the tumor
• Computed tomography scan of the neck with contrast
• Chest x-ray study
• Comprehensive chemistry panel, including liver function tests
• Complete blood count

COMPLICATIONS ON ENDOSCOPY RESECTION

• Hemoptysis subsequent to reconstruction
• Hematoma
• Airway edema
• Airway obstruction
• Dysphonia
• Aspiration
• Positive surgical margins
• Laryngeal stenosis
• Scarring
• Extrusion of Gore-Tex implant

Technorati Tags: carcinoma, glottic, radiotherapy

Thyroid carcinoma

Initial Diagnostic Approach
Nodularity of the thyroid gland is common, and palpable nodules are found more often in women than in men. The main focus of the initial evaluation is to exclude malignancy (Table 116.2).
As a basic diagnostic step, all patients with thyroid nodularity should have their thyroid function assessed with a set of function tests, particularly TSH. Ultrasound has become the gold standard for evaluation of a thyroid nodule, not only for clarifying the anatomy but also for obtaining an accurate FNA result.
Thyroidectomy: Surgical Techniques
COMPLICATIONS SURGERY FOR THYROID NODULES

* Hemorrhage and hematoma
* Seroma
* Infection
* Recurrent laryngeal nerve injury
* Superior laryngeal nerve injury
* Hypocalcemia
* Airway obstruction
* Others: pneumomediastinum, pneumothorax, hemothorax, and chyle leak



The most important prognostic parameters used include age, extrathyroidal extension, sex, size of lesion, and presence of distant metastasis.

The lymph nodes most commonly involved with thyroid metastasis are the paratracheal nodes. Following these, the metastasis pattern is one involving the level IV (52%), followed by the levels III, V, and II (45%, 33%, and 30%, respectively).
Medullary Thyroid Carcinoma
MTC differs fundamentally from thyrocyte carcinomas, not only in embryology and microscopic anatomy but also in function, tumor biology, pathogenesis, and genetics. MTC can be diagnosed at a preclinical stage by a specific secretory product, calcitonin. The hereditary variant of MTC can be identified unequivocally in about 95% of patients by genetic analysis. MTC cannot be treated with radioiodine and no multimodal treatment protocol has been proven effective in advanced and/or metastatic MTC.
Diagnosis
Most commonly, MTC is encountered in the lateral upper two thirds of the thyroid gland because C-cell concentrations are highest in this area.

Technorati Tags: thyroid, carcinoma, nodul, lymph nodes

CHEMOTHERAPY-RELATED EMERGENCIES

With administration of most chemotherapeutic drugs, granulocytopenia and thrombocytopenia regularly occur. Although granulocytopenia itself does not necessitate hospitalization, infection, characterized by fever, chills, or specific signs and symptoms, indicates a need for immediate antibiotic therapy, usually as an inpatient, if the patient has neutropenia. Blood, urine, and other fluids are cultured, and broad-spectrum, antipseudomonal antibiotics are started immediately and empirically. Administration of antibiotics is continued until neutropenia, fever, and infection resolve. Administration of granulocyte colony-stimulating factor has a role in preventing infection among aggressively treated patients but is not as helpful if initiated in the setting of established neutropenic fever.

Thrombocytopenia can be life-threatening, particularly if platelet counts decrease to less than 10,000/L to 20,000/L, in which case spontaneous and fatal hemorrhage can occur. The patient is treated with platelet transfusions until the platelet count returns to a safe range. These patients may need hospitalization because of bleeding or, in some instances, for transfusions of platelets.

Acute renal failure can occur with administration of drugs such as high-dose methotrexate or cisplatin. Patients receiving cisplatin can have severe electrolyte wasting. These conditions necessitate in-hospital evaluation and treatment by a medical oncologist and nephrologist. Allergic reactions, especially to paclitaxel, bleomycin, or cetuximab, can be severe and necessitate treatment with antihistamines, steroids, and other support. Leakage or extravasation of drugs such as vincristine or doxorubicincan cause necrosis of the skin and necessitate immediate treatment.

Nasopharyngeal Cancer & Chemotherapy

Chemotherapy is important in the treatment of nasopharyngeal cancer. It is now generally considered standard therapy for all but the few early-stage cases. The optimal timing and role of chemotherapy have yet to be determined. Metastatic, undifferentiated carcinoma, or lymphoepithelioma, of the nasopharynx is highly sensitive to chemotherapy. In four consecutive studies involving a total of 165 patients treated with cisplatin-containing regimens for metastatic lymphoepithelioma, 19% achieved a complete response, and 64% had at least a partial response. Of patients, 12% were free of disease 3 years after chemotherapy, and 14 of 165 were disease free after at least 82 months (47).
Chemotherapy also has a role in the management of squamous cell carcinoma and lymphoepithelioma when disease is local. The most compelling results are from an intergroup trial in the United States in which 147 patients were randomized to RT alone or RT with concomitant cisplatin and postradiation therapy with cisplatin and 5-FU. The study was stopped early when a significant difference in 2-year survival rate occurred in favor of the chemotherapy arm. The 3-year survival rate for the patients who had chemotherapy was 78%; the 3-year survival rate was 47% for patients who did not have chemotherapy (P = 0.005) (48). Several other studies have shown similar results with the use of concomitant chemotherapy (49).

Technorati Tags: Nasopharyngeal cancer, chemotherapy

ADVANTAGES AND DISADVANTAGES OF INDUCTION CHEMOTHERAPY

Advantages

• Drug delivery to cancer cells is unimpaired.
• Macroscopic response may predict for response of microscopic disease. Prompt elimination of micrometastases may aid in cure.
• Tumor may be downsized, allowing for more successful surgery or radiation therapy with less radical treatment.
• Patient performance status at surgery may be improved.

Disadvantages

• Original extent of tumor may be obscured.
• Performance status may decline.
• Tumor may increase during chemotherapy.
• Duration, toxicity, and cost of treatment are increased.

Technorati Tags: chemotherapy disadvantages, advantages

Paclitaxel and Docetaxel

Paclitaxel and docetaxel are among the most active drugs against head and neck cancer (10). Paclitaxel was initially isolated from the bark of the Pacific yew tree, although it is now produced synthetically. The taxanes stabilize tubulin polymers and prevent cell division. A cooperative group phase II study of single-agent paclitaxel given at fairly high doses over 24 hours to 30 patients had a response rate of 40% (11), although the drug usually is given every 3 weeks as a 3-hour outpatient infusion or weekly over an hour. The true response rate is likely slightly less than this, because larger studies of paclitaxel with cisplatin have yielded response rates of only 35%. Docetaxel has shown activity approximately equivalent to paclitaxel. These drugs are considered by many to be “first-line” agents for treatment of advanced head and neck cancer.

Technorati Tags: Paclitaxel, Paxus, Doxetaxel, Taxotere

Edit | Leave A Comment »
chemotherapy bailey
Posted in chemotherapy on July 18, 2008 by hennykartika

Principles of Chemotherapy in the Management of Head and Neck Cancer
Bruce E. Brockstein
Everett E. Vokes
(1). Alkylating agents cross-link DNA and interfere with DNA replication. Among these are nitrogen mustard, cyclophosphamide, and chlorambucil. Cisplatin and several other drugs
the antitumor antibiotics doxorubicin, bleomycin, and mitomycin C, also act by binding to DNA.
Antimetabolites actively interfere with cellular metabolism, frequently by means of inhibiting one or more target enzymes. Many agents with activity in head and neck cancer fall into this group, including methotrexate, 5-fluorouracil (5-FU), hydroxyurea, and gemcitabine.
naturally occurring vinca alkaloids, including

vincristine, vinblastine, and vinorelbine, interfere with mitotic spindle formation
The taxanes include paclitaxel and docetaxol. They are plant derivatives that stabilize microtubules and render them incapable of mitosis.
he first of these were hormonal therapies (e.g., tamoxifen and other drugs) that target the estrogen receptor. Hormonal therapies have had little use in head and neck cancer.
The ideal drugs have spectra of toxicity that do not overlap. The scheduling of drug administration takes into account possible pharmacologic interactions.

Roles of Chemotherapy in Head and Neck Cancer

Approximately one third of patients in the metastatic setting have tumor shrinkage (a partial or complete response), which lasts an average of 3 to 6 months. For patients with locoregionally advanced stage III and IV cancer, chemotherapy has two main roles: improving survival and organ preservation. Patients with nonresectable head and neck cancer who receive concurrent chemotherapy and RT rather than RT alone have had improved survival rates. For patients with resectable advanced tumors of the larynx and hypopharynx, chemotherapy followed by RT has been associated with laryngeal preservation among two thirds of patients without decreasing survival rate. Concurrent chemoradiation therapy also may allow organ preservation as well or better than induction chemotherapy with a survival rate equivalent to that of surgery.

Technorati Tags: chemotherapy, head and neck, oncology

Cisplatin - Carboplatin

Cisplatin, which has been a mainstay in the treatment of head and neck cancer, frequently is used to treat cancer of the head and neck. Its antitumor activity results from intracellular binding of the activated, positively charged form with a nucleophilic site on DNA to form bifunctional covalent links that interfere with normal DNA function (1). Cisplatin usually is administered over 2 to 6 hours in doses of 60 to 120 mg/m2, with similar efficacy reported for this entire dosage range. Renal toxicity is common and includes mild to moderate azotemia and electrolyte wasting, particularly of magnesium and potassium. Other toxic reactions include nausea and vomiting, peripheral neurotoxicity, ototoxicity, and cumulative myelosuppression if several cycles of the drug are administered. For single-agent doses ranging from 60 to 120 mg/m2 given every 3 to 4 weeks, partial response rates of approximately 15% to 30% are achieved.
Because of the toxicity of cisplatin, in particular its dose-limiting nephrotoxicity and neurotoxicity, analogues of the drug have been developed with the goal of preserving the antitumor activity of the drug and decreasing its toxic effects. Carboplatin has decreased nephrotoxicity and neurotoxicity. Its dose-limiting toxicity is myelosuppression. Another advantage of this compound is a comparable ease of administration. Because nausea and vomiting are reduced, carboplatin can be given easily on an outpatient basis and without vigorous hydration. It is active against cancer of the head and neck, but slightly less so than is cisplatin. Carboplatin is now commonly used, particularly in the palliative setting, in which minimizing side effects and hospital time is essential (14). An additional platinum compound, oxaliplatin, is currently in clinical trials for head and neck cancer.

Technorati Tags: Chemotherapy, Cisplatin, Carboplatin

5-Fluorouracil

5-Fluorouracil is an S phase, specific uracil analogue that can be activated with two major intracellular pathways: (a) sequential phosphorylation and incorporation into RNA or (b) activation to 5-fluorodeoxyuridine monophosphate, which blocks both the enzyme thymidylate synthase and the conversion of uridine into thymidine compounds. Cells are depleted of thymidine and cannot synthesize DNA. Many other drugs have been shown to interact with 5-FU, and trials aimed at increasing its activity by means of modulating its intracellular metabolism have been conducted. The most important side effects are myelosuppression, mucositis, diarrhea, dermatitis, and cardiac toxicity. Used as a single-agent intravenous bolus to treat patients with head and neck cancer, 5-FU has limited activity. A response rate of 13% was found in one large, randomized trial (13). 5-Fluorouracil can be substantially more active administered in a 5-day continuous infusion and clearly adds to the response rate of cisplatin.

Technorati Tags: chemotherapy, 5-fluorouracil, side effect

Methotrexate

Methotrexate is an antimetabolite that interferes with intracellular folate metabolism by binding to the enzyme dihydrofolate reductase. This inhibits conversion of folic acid to tetrahydrofolate. The result is cellular depletion of reduced folates and inhibition of DNA synthesis. This drug is active only during the S phase of the cell cycle. It selectively affects tissues with more rapid cell turnover. The side effects of methotrexate can be minimized by supplying reduced folates in the form of leucovorin within 36 hours after exposure to the drug. As a single agent, methotrexate usually is given in weekly doses of 40 to 50 mg/m2. Toxic reactions include myelosuppression, mucositis, dermatitis, nausea, vomiting, diarrhea, and hepatic fibrosis. These toxicities are exacerbated with high-dose regimens unless leucovorin rescue is administered. Renal injury occurs with high-dose schedules.
Methotrexate produces a partial response rate of approximately 10% (9,10); the response duration ranges from 1 to 6 months. Improved response and survival rates are not consistently achieved with high-dose methotrexate regimens, but toxicity increases. Therefore, high-dose methotrexate is not used. Although single-agent methotrexate sometimes is used, other drugs or combinations, especially those containing 5-FU, paclitaxel, or cisplatin lead to higher response rates. Survival rate is not clearly improved with these combinations, and toxicity can be greater than that of single-agent therapy. Thus, methotrexate is the minimal standard treatment of patients having chemotherapy (8). Although it is sometimes still used as a control arm in randomized trials, currently it is not generally used as first-line therapy.

BENEFITS AND MECHANISMS OF CHEMORADIOTHERAPY

Drugs and irradiation can be active against different tumor cell subpopulations based on cell-cycle specificity, pH, and oxygen supply. Cells resistant to one modality of treatment can be eradicated by the other.
Combination therapies can increase tumor cell recruitment from G0 into radiation therapy-responsive cell-cycle phase.
Tumor shrinkage can decrease interstitial pressure and, therefore, increase drug and oxygen delivery.
Early eradication of tumor cells prevents emergence of drug or radiation resistance.
Cell-cycle synchronization increases the effectiveness of both therapies.
Chemotherapy inhibits repair of sublethal radiation damage and inhibits recovery from potentially lethal radiation damage.

Technorati Tags: chemoradiotherapy, cell-cycle, oxygen

Edit | Leave A Comment »
Combination Chemotherapy
Posted in chemotherapy on July 18, 2008 by hennykartika

most combinations have been based on methotrexate or cisplatin, and most recently on cisplatin or carboplatin, paclitaxel or docetaxel, bleomycin and 5-FU.
Combinations of drugs are thought to be superior to single agents because cells resistant to one agent may be sensitive to another. One of the “standard” combination regimens has been cisplatin followed by a 4- to 5-day continuous intravenous infusion of 5-FU. In the care of patients with recurrent disease, it has had reproducible response rates ranging from 30% to 40% (13,14). In the neoadjuvant setting of locally advanced, nonmetastatic disease, impressive response rates of about 80%, with 10% to 40% complete responses, have occurred (6,10,23,24). The combination of cisplatin and 5-FU was compared with each of these drugs delivered as single agents in a three-arm randomized trial (13). Although the response rate of the combination (32%) was significantly higher than that of cisplatin alone (17%) or 5-FU alone (13%), no significant difference was seen in the median survival period of 5 to 6 months for all groups. In a three-armed, randomized trial, the Southwestern Oncology Group (14) compared cisplatin and 5-FU with a combination of carboplatin and 5-FU (postulated to be equally active but less toxic) and single-agent methotrexate as standard therapy. Both cisplatin and carboplatin combined with infusion of 5-FU had a better response rate than did methotrexate alone. Both combinations were more toxic, and survival rate was not affected in any of the arms.

The taxanes are commonly used in combination regimens. The Eastern Cooperative Oncology Group (ECOG) directly compared cisplatin (75 mg/m2) plus paclitaxel (175 mg/m2) every 21 days to cisplatin (100 mg/m2) and 5-FU (1,000 mg/m2 daily infusion, days 1-4) every 21 days as first-line therapy in 194 patients with advanced head and neck cancer (25). In a preliminary report, the cisplatin–paclitaxel combination was associated with similar median (9 vs. 8 months) and 1-year survival rates (30% vs. 41%), but a more favorable toxicity profile. In the palliative setting, carboplatin is often substituted for cisplatin in combination with a taxane. Several other three-drug or four-drug combination regimens containing taxanes have shown high response rates and are under development.
An analysis of the available, appropriately conducted, randomized chemotherapy trials had the following conclusions about combination regimens (8).

Combinations produce statistically significantly higher response rates than do single agents, including methotrexate.
In no comparison group (single agent or combinations with taxanes excluded) is survival time meaningfully lengthened.
The toxicities of cisplatin and infusional 5-FU, especially nausea and vomiting, are significantly greater than those of single agents.

The benefit of CRT must be weighed against the toxicity inherent in its use. The risk of acute mucositis, dermatitis, and chemotherapy-specific side effects is greater than with either mode of therapy alone. The latest generation of studies continues to show improved survival rates with aggressive CRT. This advantage is maintained even when chemotherapy is added to hyperfractionated RT, so the benefit of chemotherapy is not solely because of the more intensive treatment (hyperfractionation) but to a true radioenhancing effect



Technorati Tags: Combination Chemotherapy, Cisplatin, Methotrexate, 5-FU