Transcript Appearance Of Seasonal Allergens

#1008
New Strategies in Treatment of Lung Cancer
November 9 to 12
Patrick Ross, Jr. MD, PhD
Assistant Professor of Surgery
Division of Surgical Thoracic Oncology
The Ohio State University Medical Center &
The James Cancer Hospital and Solove Research Institute
Gregory A. Otterson, MD
Associate Professor of Internal Medicine
Division of Hematology and Oncology
The Ohio State University Medical Center &
The James Cancer Hospital and Solove Research Institute
Gregory A. Otterson, MD
Associate Professor of Internal Medicine
Division of Hematology and Oncology
The Ohio State University Medical Center &
The James Cancer Hospital and Solove Research Institute
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Profile
Mr. Perkins
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55 year old male
Smoker
Hemoptosis
Photodynamic therapy
2 cycles of chemotherapy
Diagnosis: Large T3 N2 tumor
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New Treatment Strategies In
The Treatment Of Lung Cancer
• Multimodality treatment for locally
advanced NSCLC
- Surgery
- Radiation
- Chemotherapy
• Novel agents
- SCLC - antisense bcl2
- NSCLC - farnesyltransferase
inhibitors
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Lung Cancer Statistics,
1999
• Greatest cause of cancer death
worldwide
- 921,000 deaths worldwide
- 158,900 US deaths (90,900 men,
68,000 women)
• 28% of US cancer deaths
(14% cancer cases)
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Lung Cancer Treatment Stage And Type Specific
• Non-small cell lung cancer (NSCLC)
- ~80% of lung cancer
- Principally surgically treated
- Chemotherapy and radiation therapy
added in specific circumstances
• Small cell lung cancer (SCLC)
- ~20% of lung cancer
- Principally chemotherapy
+/- radiation therapy
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Locally Advanced NSCLC
• Stage IIIB - Generally unresectable
- Either bulky primary tumor involving
critical mediastinal structures, pleural
effusion or contralateral mediastinal
lymph node involvement
• Chemotherapy added to radiation therapy
improves control and survival
- Concurrent vs. sequential?
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Locally Advanced NSCLC
• Stage IIIA - Theoretically resectable
- Ipsilateral mediastinal lymph nodes
involved
• Surgery is principal modality in most
centers
- Post-operative radiation improves local
controls
- Post-operative chemotherapy has not
been dramatically successful
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Stage IIIA NSCLC
• Questions asked in clinical trials
- ? Pre-op chemotherapy
- ? Pre-op radiation therapy
- ? Pre-op chemo-radiotherapy
- ? Role of surgery
• These questions remain open
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Stage IIIA NSCLC
• Balance risks with benefits of
aggressive treatment
- Improved local / systemic control
- Increased treatment related morbidity
and mortality with combined treatment
• Prognostic / treatment factors
- Weight loss (5-10%), performance
status, age, comorbid conditions
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OSU Trial For Resectable
Stage IIIA NSCLC
• Pre-operative chemotherapy for three
cycles (paclitaxel and carboplatin)
• Pre-operative radiation (to 4500 cGy) with
a novel (Gadolinium-Texaphyrin)
radiation sensitizer
• Curative resection planned after
completion of radiation
• If incomplete resection, post-op radiation
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Novel Drug Strategies
• Apoptosis - many chemotherapeutic
drugs induce cell death by initiating
a cellular suicide pathway in cancer
cells (called apoptosis)
• Some cancers (including most SCLC)
overexpress an oncogene (bcl2) that
protects cells from apoptosis
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Bcl2 Family Of Proteins
• Family of proteins that are involved in
apoptotic pathways (some pro-, others
anti-apoptotic)
• Bcl2 family members can homo- and
hetero-dimerize with each other
• Susceptibility to programmed cell death
(apoptosis) depends on relative ratio of
homo- and hetero-dimers
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Bcl2 Antisense Therapy
• Chemotherapy induces cell death
through apoptosis
• Bcl2 protects cells from apoptotic death
• In theory, chemotherapy should be more
effective if bcl2 is inhibited
• Therefore, use bcl2 antisense (synthetic
oligonucleotide directed against the
bcl2 messenger RNA molecule)
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Bcl2 Antisense In SCLC
• Patient population: resistant SCLS
(Either progressive disease on
treatment or relapse within 3 months)
• G3139 (bcl2 antisense) via continuous
IV infusion X 7 days
• Paclitaxel 175 mg / m2 over 3 hours,
day 6 q 3 weeks
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Novel Drug Strategies
• Ras is an oncogene that is mutated
in many different cancers (~90% of
pancreatic ca, ~50% of colon ca
and ~30% of NSCLC)
• Ras (normal and mutant) requires
association with the cell membrane
via a cholesterol precurser for
activity
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Inhibit Ras Activity Through
Its Membrane Association
• HMG-CoA reductase inhibitors were
attempted without remarkable
success
• Inhibition of the farnesyl-transferase
enzyme has been pursued with
better pre-clinical ad early clinical
activity
• Single agent and combination trials
are now underway (including one at
OSU)
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Improvement In
Lung Cancer Survival?
• Better local control
- Improved surgical technique
- Improved preparation / selection
of surgical patients
- Improved radiotherapy technique
and radiation sensitizers
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Improvement In
Lung Cancer Survival?
• Better control of systemic disease
- Application of current
chemotherapeutic agents in
combination with surgery and / or
radiation therapy
- Novel chemotherapeutic agents,
designed to attack specific genetic
defects in tumor cells (for example,
bcl2 antisense and farnesyltransferase
inhibitors)
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Summary
Mr. Perkins
Diagnosis: IIIA non-small lung cancer
Treatment:
- Photodynamic therapy
- Chemotherapy
- Right pneumonectomy
Follow-up:
- Operation went smoothly
- Further radiation and chemotherapy
Prognosis: Good
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Patrick Ross, Jr. MD, PhD
Assistant Professor of Surgery
Division of Surgical Thoracic Oncology
The Ohio State University Medical Center &
The James Cancer Hospital and Solove Research Institute
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Profile
Joseph Tigerina
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61 year old male
Former smoker
Newly identified left upper lobe mass
Presented to family physician with
left shoulder and back pain
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Profile
Joseph Tigerina
Symptoms
- No cough or hemoptsis
- Some fatigue
- No weight loss
Evaluation
- CT scan and CT needle guided biopsy
- MRI
- PET scan
Diagnosis: Non small cell carcinoma
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Non Small Cell
Lung Cancer
• Can the tumor
be resected?
• Can the patient
undergo
resection?
• What can be
done to improve
the outcome?
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NSCLC: Diagnosis
And Staging
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Chest x-ray
CT scan chest
Distant metastasis evaluation
Bronchoscopy
Trans thoracic needle biopsy
Mediastinoscopy
VATS
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Solitary Pulmonary Nodule:
PET Scan
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Surgical Management
Of Stage 1 And 2
• Wedge resection vs lobectomy
• Node sampling N1 and N2
• Refer for adjuvant trials:
evaluation of chemotherapy for
early stage
• Appropriate surveillance
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Superior Sulcus Tumors
• Arm pain
• Arm
parathesias
• Shoulder pain
• Horner’s
syndrome
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NSCLC Induction Therapy:
Stage IIIA
• Surgical staging
• Chemo or
Radiation/chemo
• Evaluate for
distant disease
• Nutrition
• Pulmonary rehab
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Induction Therapy
• Radiation alone
• Chemotherapy alone
• Radiation and chemotherapy:
simultaneous vs sequential
• Radiation, and / or chemotherapy
with PDT
• Pulmonary rehabilitation
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Pulmonary Resection In
The High Risk Patient
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FEV 1 < 0.8
Hypoxemia
Hypercarbia
Steroid dependent
Elderly
Previous pulmonary
resection
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Pulmonary Rehabilitation
• Prepare patient for
resection
• Decrease hospital
stay
• Enhance recovery
• Promote sense of
well being
• Minimize impact of
chronic illness
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Summary
Joseph Tigerina
Surgical procedure
- Left upper lobe resection for
non small cell cancer
- Stage 1b lesion - all nodes were
negative
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Summary
Joseph Tigerina
Follow-up treatment
• Given staging, treatment options
are:
- Surveillance
- Adjunctive chemotherapy within
a defined protocol
Prognosis: Good
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NEXT WEEK
#1009 Evaluation & Management of
Atrial Fibrillation
November 16 to 19
Stephen F. Schaal, MD
Professor of Internal Medicine
Division of Cardiology
The Ohio State University Medical Center
Robert Hoover, MD
Assistant Professor of Internal Medicine
Division of Cardiology
The Ohio State University Medical Center