TRIPASS XR تري باس

 

noticed a

20-pound weight loss within three months, although she

attributed this to changes in her diet. She was not complaining of any coughing. There was no shortness of breath. The

evaluation with chest radiogram demonstrated the presence of a large mass in the right parahilar region with

extension to the mediastinum and significant mediastinal

adenopathy with narrowing of the trachea and its displacement to the left by the mass. The follow-up PET-CT scan

confirmed presence of that large mass and no other areas

of abnormality within the abdomen or pelvis. Patient also

had a brain MRI which showed no evidence of metastatic

disease. After that, the patient had a bronchoscopic evaluation and a biopsy of the mediastinal mass. Pathology came

back positive for small cell lung carcinoma histology. Having disease only limited to the chest and mediastinum, the

patient was diagnosed with limited stage SCLC. Peripheral

blood chemistry, LDH, and counts were normal. What features of M.W.’s disease are suggestive for SCLC?

M.W.’s chief complaints were heartburn and pain in the upper

right side of her abdomen, not necessarily common symptoms

of SCLC. Location of the tumor is a determining factor in specific symptoms that a patient can experience, and can serve as

an indicator of the invasiveness of the disease. Although M.W.

did not complain of cough, her presentation is representative

of patients diagnosed with this disease in that the tumor was

centrally located with spread to the mediastinum. She also experienced weight loss, and although she attributed this to her diet,

it is a symptom experienced by patients with rapidly growing

disease, and associated with appetite suppression.

CASE 94-3, QUESTION 2: What potential complications

might patients such as M.W. experience during the course

of their disease?

M.W. did not experience all of the symptoms that are frequently found in patients. Fatigue, especially together with

decreased physical activity, is a common complaint as well as

hemoptysis.62 Owing to the central location of most of these

tumors, approximately 10% of patients can experience superior

vena cava syndrome (SVCS). This is a very serious complication and requires immediate medical attention as a result of the

growing tumor impinging upon the superior vena cava. This can

restrict blood return to the heart, resulting in head and facial

swelling.63,64

For a visual of the superior vena cava

syndrome, go to http://thepoint.lww.

com/AT10e.

One-third of patients have some degree of atelectasis

present.65 A peripheral location or chest wall involvement by

the tumor is uncommon. Rarely, SCLC presents as a solitary

pulmonary nodule.

Patients with SCLC frequently experience paraneoplastic

syndromes as a result of their disease, and these often differ

from patients who have NSCLC. For example, patients with

NSCLC have a higher tendency to develop hypertrophic pulmonary osteoarthropathy and hypercalcemia. On the other

hand, patients with SCLC have higher incidence rates for syndrome of inappropriate antidiuretic hormone (SIADH), Cushing syndrome, and neurologic paraneoplastic syndrome. The

serum concentrations of antidiuretic hormone are often elevated

in SCLC, but few of these cases fulfill the criteria for SIADH and

are mostly asymptomatic. In some cases, ectopic production of

atrial natriuretic factor contributes to the disorder in sodium

homeostasis. Because SCLC is usually responsive to cytotoxic

agents, the treatment of choice for hyponatremia is chemotherapy. If further management is needed (i.e., if the cancer is nonresponsive to chemotherapy or symptomatic), fluid restriction,

intravenous hypertonic saline, and treatment with demeclocycline are options, depending on severity.1 The serum concentrations of adrenocorticotropic hormone are elevated in approximately half of patients with lung cancer, but Cushing syndrome

develops in only 5% of those with SCLC. Low serum sodium and

Cushing syndrome are both poor prognostic indicators for the

disease.1

2220Section 17 Neoplastic Disorders

Unlike M.W., most patients already have metastatic disease at

diagnosis, and the most common sites include bone, liver, adrenal

glands, and brain. Bone pain may or may not occur, depending

on the nature of the metastases to the afflicted area. Patients with

hepatic and adrenal lesions do not usually experience symptoms,

even if they have elevations of bilirubin, alkaline phosphatase, or

hepatic transaminases. In contrast, brain metastases are symptomatic in more than 90% of cases, and patients can often present

with central nervous system complications (e.g., seizures) as the

first sign of the disease.1

TREATMENT MODALITIES FOR SMALL CELL

LUNG CANCER

CASE 94-3, QUESTION 3: M.W. reads about various treatments for her disease online. What is the utility for each of

the three treatment modalities (i.e., surgery, radiation, and

chemotherapy) for the treatment of her disease?

SURGERY

As mentioned earlier, surgery has a very limited role as part of

the treatment for patients with SCLC. In general, patients with

tumors larger than 3 to 7 cm and presence of any disease in the

lymph nodes or distant metastases do not benefit from surgery.66

The percentage of patients who fit this category is less than 5%. If

surgery is chosen, the procedure usually includes lobectomy with

mediastinal nodal dissection and sampling. Thereafter, patients

would receive adjuvant radiation and chemotherapy and then

prophylactic cranial irradiation as described in the subsequent

sections.

RADIATION

SCLC is responsive to radiation therapy; therefore, it is useful in treating patients with limited stage disease. These treatments are usually given as fractionated doses over the course

of 2 to 4 weeks, and total dosage targets range between 45 and

70 Gy. Three-dimensional conformal radiation (intensity modulated radiation therapy) is the preferred method, and the radiation is delivered from an external source concurrently with

multidimensional imaging to assure tumor movement of less

than 1 cm is achievable (movement as a result of breathing

during the procedure). See http://www.slideshare.net/fovak/

igrt-srt-for-lung-cancer for more information.67–69 In addition

to their cytotoxic effects, many chemotherapeutic agents also

sensitize tumors to radiation. Hence radiotherapy should start

concurrently with chemotherapy, usually at the first or second

cycle. Due to the high incidence of metastases to the brain (i.e.,

greater than 50% of patients with SCLC), prophylactic cranial

irradiation is the standard of treatment for patients with limited

stage and extensive stage diseases. The total dosage for this ranges

between 25 and 30 Gy given for 10 to 15 fractions.70,71

CHEMOTHERAPY

The proliferative indices for SCLC cells are high, and early

metastatic spread is common. Therefore, systemic chemotherapy is the treatment of choice because it is effective for tumor

cells progressing through the cell cycle and its utility for treating metastases. Shown in Table 94-769,72−75 are the commonly

used representative first-line treatment regimens for limited stage

and extensive stage diseases. In general, most of the regimens

are platinum-based combinations with etoposide or, less commonly, irinotecan (the latter proven to be efficacious in Japanese

patients). If a tumor response is observed, the benefit is usually seen early during the treatment course. Prolongation of

TABLE 94-7

Representative Chemotherapy Regimens for Small Cell

Lung Cancer

Limited Stage SCLC (maximum 4–6 cycles)

Cisplatin, day 1

Etoposide, days 1, 2, 3, and then every 21 days69

Carboplatin, day 1

Etoposide, days 1–4, then every 21 days72

Extensive Stage SCLC (maximum 4–6 cycles)

Cisplatin, day 1

Etoposide days 1–4, then every 21 days72

Carboplatin, day 1

Etoposide, days 1, 2, 3, then every 21 days73

Cisplatin, day 1

Irinotecan days 1, 8, 15, then every 28 days74

Cisplatin, day 1

Irinotecan days 1, 8, then every 21 days75

Chemotherapy for Relapsed Disease58

Clinical trial preferred

If relapse occurs <2–3 months after first-line and PS 0–2: ifosfamide,

paclitaxel, docetaxel, gemcitabine, irinotecan, or topotecan

If relapse occurs >2–3 months up to 6 months: topotecan (oral or IV),

irinotecan, paclitaxel, docetaxel, oral etoposide, vinorelbine,

gemcitabine, or cyclophosphamide/doxorubicin/vincristine

If relapse occurs >6 months: original regimen

PS, performance status; SCLC, small cell lung cancer.

treatment beyond six cycles is usually not recommended for

this disease because the maximum effect of the treatment is

achieved in this time frame. Further, toxicity after treatment

with these agents accumulates and diminishes the overall benefit to the patient beyond six courses76,77 Hence, treatment is

usually stopped after four to six cycles and the patient is closely

monitored for recurrence of the disease afterward.

As mentioned previously, SCLC has a very high rate of recurrence; therefore, second-line therapy is usually implemented.

Several choices of agents are available as shown in Table 94-7, and

the selection is dependent on the overall condition of the patient

(e.g., performance status, toxicity from previous regimen) and

the length of time after the first line regimen was completed.

Many of these agents are given as single agent therapy except

for the CAV regimen. In general, a recurrence that occurs within

6 months of treatment with first-line therapy is considered resistant and other agents are selected. If recurrence occurs after

6 months, then the same agents used for the first-line regimen

may be used again. To date, no targeted agents are approved for

use in treating SCLC.

In conclusion, M.W.’s disease would not be a good candidate

for surgical removal because there is lack of proven benefit. Small

cell lung tumor cells proliferate rapidly; therefore, they are usually responsive to chemotherapy and radiation treatment. This

systemic therapy would also be favored because the tumor tends

to metastasize quickly and it provides a way to eradicate disease