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LUNG, NSC

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Should we treat or not???
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Taxol/Carboplatin & concurrent XRT
Cisplatin/Etoposide & concurrent XRT(Intergroup Trial 0160)
Cisplatin weekly & concurrent XRT
Taxol/Carboplatin
Docetaxel/Carboplatin
Cisplatin/Gemzar
Docetaxel/Gemzar
Weekly Docetaxel
Weekly Navalbine
Cisplatin/Navalbine

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CISPLATIN + ETOPOSIDE & CONCURRENT XRT
(Intergroup Trial 0160)


CISPLATIN 50 mg/m2 IV DAYS 1, 8, 29, 36
ETOPOSIDE 50 mg/m2 IV DAYS 1-5 & 29-33
XRT: 45 Gy @ 180 cGy/day over 5 weeks

REF: J. Thoracic & Cardiovascular Surgery 121(3):472,2001
The initial results of phase II intergroup trial coordinated by the Southwest Oncology Group (SWOG). Pathologically proven & previously untreated NSCLC involving the superior sulcus with either a T3 or T4 primary tumor.

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TAXOL + CARBOPLATIN & concurrent XRT
paclitaxel 45 mg/m(2) over 1 h;
carboplatin AUC=2;
six weekly cycles
+ XRT 60 Gy to the primary tumor & regional LN (40 Gy over 4 weeks) followed by a boost to the primary tumor (20 Gy in 2 weeks).

After the initial phase of concurrent chemoradiation, patients received an additional 4 cycles of Taxol 175 mg/m(2) over 3 h + carboplatin AUC=6 Q 3 weeks.

REF=Lung Cancer 2001 Feb;31(2-3):257-265
N=30 locally advanced inoperable NSCLC; ORR=76.7%. At the median follow-up time of 13.1 months, the median survival time = 14.5 months (95% CI, 10.59-18.48). The median PFS=10.5 months (95% CI, 7.72-13.28). Major toxicity:hematologic. Grade 3 esophagitis=10%.

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Weekly Cisplatin

CISPLATIN 30 mg/m2 Qweek while receiving radiation therapy. Then may use other systemic regimen (combination chemotherapy).

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Taxol-Carboplatin 3 hours , AUC of 6

Taxol 175 mg/m2 CIV over 3 h*
Carboplatin AUC=6 (IVPB as a 1-mg/min infusion.)

Repeat every 4 weeks.

*Dose adjusted for 3 hour infusion

Ref. Paul D.M., Johnson D.H., et al.: Proc. ASCO 1994; 13:352
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DOCETAXEL + CARBOPLATIN

DOCETAXEL 75-100 mg/m2
CARBOPLATIN AUC=6
Q3 weeks

REF:
Lung Cancer 2001 Jun;32(3):281-287
Semin Oncol 2001 Jun;28(3Suppl 9):10-14
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GEMZAR + CISPLATIN

GEMCITIBINE 1000 mg/m2 DAYS 1,& 8 Q21 days
CISPLATIN 100 mg/m2 DAY 1 Q21 days
***This regimen is indicated as first line therapy for inoperable IIIA/IIIB or IV.


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GEMCITIBINE 1000 mg/M2 Days 1,8,15
CISPLATIN 100mg/M2 day 15
28 day cycle

Response Rate of 52% PR + CR: 1 yr Sur 61%
RP Abratt et al. JCO 15: 744-749. 1997

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Taxol-Carboplatin 3 hours

Taxol 175 mg/m2 CIV over 3 h*
Carboplatin 300 mg/m2 IV as a 1-mg/min infusion.

Repeat every 4 weeks.

*Dose adjusted for 3 hour infusion

Ref. Paul D.M., Johnson D.H., et al.: Proc. ASCO 1994; 13:352
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ADVANCED / METASTATIC Phase II

GEMCITABIBE/DOCETAXEL

GEMCITABIBE 800 mg/m2 infuse over 30 minutes DAYS 1,8,15
DOCETAXEL 100 mg/m2 infuse over 1 hour following gemcitabine on DAY 1

Repeat Q4 weeks

REF: ASCO 2000

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Weekly DOCETAXEL (elderly population)

DOCETAXEL 36 mg/m2 infuse over 1 hour

Note: dexamethasone 8 mg PO given 12 hours prior, immediately prior to, & 12 hours following docetaxel infusion.

Repeat weekly X 6 weeks followed by 2 weeks without treatment.


REF: ASCO 2000
19% Objective Response ; 36% minor response or stable disease. (Response by PS: ECOG0-1=26%,ECOG2=7%)

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CISPLATIN + NAVALBINE

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PET scanning in lung cancer

Comparing PET & CT in mediastinal Staging of Lung Cancer:

Pieterman (NEJM 343:254;2000)
N=102 PET Sensitivity=91%, Specificity=86%; CT(size criteria 1.0 cm) Sensitivity=75%, Specificity=66% (P<0.001)

Vansteenkiste (Clin Pos Imag 2:223, 1999)
N=105 PET Sensitivity=89%, Specificity=99%; CT(size criteria 1.5 cm) Sensitivity=79%, Specificity=54% (P<0.0003)

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Metastatic disease:

PET useful to distinguish adrenal metastasis from adrenal hyperplasia or enlarged adrenal gland that may be noted on CT scans.

> 10% of the pts who undergo PET scanning are shown to have distant metastasis that was not detected by CT scans.
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TREATMENT SUMMARY
STAGE I
>>Primary Therapy: Surgery

>>Unresectable patients: Those with inoperable stage I disease & with sufficient pulmonary reserve can be considered for XRT with curative intent. A report of pts age>70 years who had resectable lesions >4 CM (but medically inoperable or refused surgery) 5-YR survival following XRT with curative intent was comparable to a historical control group of patients of similar age resected with curative intent.
REF=Radiotherapy & Oncology 13(2): 83, 1988.

>>Role of adjuvant XRT: A meta-analysis of 9 randomized trials evaluating postoperative XRT versus surgery alone showed a 7% reduction in overall survival with adjuvant XRT in patients with stage I or II disease.
REF=Lancet 352(9124): 257, 1998.
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STAGE II:
>>Primary Therapy: Surgery

>>For inoperable patients: Patients with sufficient pulmonary reserve may be considered for XRT with curative intent. Up to a 20% 3-year survival rate may be acheived. In the largest retrospective series reported to date, 152 patients with medically inoperable NSCLC treated with definitive XRT had 5-year OS=10%; however, the 44 patients with T1 tumors had an actuarial DFS=60%.
REF=JCO 8(5): 362, 1985.

>>Role of adjuvant XRT: A meta-analysis of 9 randomized trials evaluating postoperative XRT versus surgery alone showed a 7% reduction in overall survival with adjuvant XRT in patients with stage I or II disease.
REF=Lancet 352(9124): 257, 1998.
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STAGE IIIA
>>Primary Therapy: Surgery (curative intent)
>>Role of induction chemotherapy is still under investigation.
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STAGE IIIB
>>Primary Therapy: Induction chemotherapy or chemoradiotherapy. Patients with unresectable stage III who are candidates for combined chemotherapy & radiation, the duration of chemotherapy should be no more than 8 cycles. The role of posttreatment surgery in initially unresectable patients who have an excellent response to chemotherapy/radiotherapy is undefined, with the possible exception of Pancoast tumors. In patients with unresectable stage III disease, chemotherapy may best be started soon after the diagnosis of unresectable NSCLC has been made. Delaying chemotherapy until performance status worsens or weight loss develops may negate the survival benefits of treatment. (ASCO guidelines 1997)
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STAGE IV
Primary Therapy: chemotherapy is superior to BSC in eligible patients. Can improve survival a few months depending on the study & improved QOL is also achieved. Good PS patients include Hgb>11 gm/dL, nl LDH, nl Ca, and having 1 or less metastatic site!!! Chemotherapy should be administered for no more than 8 cycles. Chemotherapy should be initiated while the patient still has good performance status. Delay in the initiation of chemotherapy could potentially prove detrimental. Chemotherapy may also impart palliative benefits in a proportion of symptomatic patients when initiated early in the course of illness.
CNS METASTASIS. In patients with controlled disease outside of the brain who have an isolated cerebral metastasis in a resectable area, resection followed by whole-brain XRT is superior to whole-brain XRT alone.