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Regional Oncology Update - Fall 2004 (click here to download as a PDF)

Chemotherapy & Radiation Therapy in Early Stage Non-Small Cell Lung Cancer (NSCLC)

According to the American Cancer Society, 173,700 new cases of lung cancer will be diagnosed in 2004. In the United States, lung cancer has been the number one cause of cancer death since 1988 for both men and women with 164,440 deaths expected in 2004. The number of deaths from lung cancer exceeds the combined death rates from breast, colon and prostate cancer. The overall 5-year relative survival rate is 15% but when lung cancer is treated during the localized stage the survival rate climbs to about 50%.

Sixty-seven percent of persons diagnosed with a surgical-pathological IA staging and fifty- s rcent of persons diagnosed with a IB tumor are expected to survive ≥ 5 years after complete resection (p<0.01). Unfortunately, only 16% of lung cancer is diagnosed in this early stage. (See Graph A.)

With the above statistics in mind, I would like to discuss a few studies showing benefit of chemotherapy in early stage non-small cell lung cancer as well as other studies addressing the efficacy of treatment modalities.

A Randomized Trial of Postoperative Adjuvant Therapy in Patients with Completely Resected Stage II or IIIa Non-Small-Cell Lung Cancer. NEJM 2000; 343: 1217-1222

In this trial, 488 patients were randomized to either receiving 50.4 cGy in 28 daily fractions alone or in combination with Cisplatin and Etoposide every 28 days for 4 cycles. The follow up was 44 months. Treatment associated mortality was 1.2% in the radiation arm, and 1.6% in the combination arm with a median survival of 39 months and 38 months respectively. Intra-thoracic disease recurred within the radiation field in 30/234 of the radiation arm (13%) and 28/236 of the combination arm (12%). Thus adjuvant radiotherapy and chemotherapy compared with radiotherapy did not decrease the risk of intra-thoracic recurrence or prolong survival in completely resected stage II

Cisplatin-Based Adjuvant Chemotherapy in Patients with Completely Resected
Non-Small-Cell Lung Cancer. NEJM 2004; 350:351-360

Of the 1,867 persons enrolled in this trial: 36.5% had pathologic Stage I disease, 24.2%, Stage II, and 39.3%, Stage III. They were randomized to 3 or 4 cycles of chemotherapy or to an observation only arm. The following drugs were used with cisplatin: etoposide in 56.5% of patients, vinorelbine in 26.8%, vinblastine in 11%, and vindesine in 5.8%. Half of the patient population had chemotherapy. There was a 56 month median duration of follow up. The 5-year survival rate was 44.5 % in the chemotherapy arm and 40.4% in the observation arm (469 deaths versus 504). Disease free survival rate was 39.4% versus 34.3% at 5 years (518 events versus 577).

The conclusion reached in Multidisciplinary Management of Lung Cancer. NEJM 2004; 350: 379-392 was that >60-70% of persons treated with surgical resection and chemotherapy experienced a 5-year survival and >40-50% of those treated with surgical resection and chemotherapy, with or without radiation, experienced a 5-year survival. The 5-year survival after surgical resection of a T2N1M0 (Stage IIB) is 39%. Based on the IALT study, a 4.1% increase in survival is expected and the option of adding chemotherapy should be offered to persons preparing to undergo lung cancer treatment. To understand the significance of this small percentage increase in survival, remember there are approximately 40,000 cases, each year, of lung cancer stage IB, and II which translates to at least 2000 lives saved.

Randomized Phase III Trial of Adjuvant Chemotherapy with UFT (Uracil-Tegafur) for Completely Resected Pathological Stage I (T1N0M0, T2N0M0) Adenocarcinoma of the Lung: a Japanese study presented at ASCO 2003.

The conclusion of this trial is that oral administration of UFT (not currently available in the United States) in a postoperative adjuvant setting yields a significant improvement in survival in patients with pathological stage I adenocarcinoma of the lung, especially stage IB (T2N0M0).

Other trials presented at ASCO 2004 worth noting are the following. One trial (CALGB 9633) for lung cancer stage IB, T2, N0, found that the oncologist’s “friendly” regimen of carboplatin/paclitaxel provided an absolute benefit of 12% at four years. The second trial was under the auspices of the National Cancer Institute of Canada clinical trials group, for stage IB and stage II lung cancer. Cisplatin and navelbine were given with the yield of a 15% absolute survival advantage at 5 years.

To better understand the role of radiation therapy in early stage non-small cell lung cancer post-op as adjuvant treatment, we have the PORT meta-analysis. This analysis includes 2,128 patients from 9 randomized trials. It was found that of the 1,056 patients treated with radiation therapy, 707 died; and, of the 1072 patients treated with surgery 661 died. The conclusion was radiation therapy for stage I and II has a detrimental effect on survival with 21% relative risk, and 7 % absolute reduction in survival at 2 years. A subgroup analysis suggests that this adverse effect was greatest for patients with stage I/II, N0, N1. At the same time we realize 15% of patients had radiation therapy in the IALT study mentioned above. Thus it is still a controversial issue though at this time most medical oncologists and radiation oncologists would not add radiation to stage I and II non-small cell lung cancer.

In closing, the most recent NCCN non small cell lung guidelines call for adjuvant chemotherapy for persons who are young, have a poorly differentiated tumor and are staged T1, N0. Adjuvant chemotherapy is advised for all persons with T2,N0 tumors. If the surgical margins are positive, chemotherapy is recommended in combination with radiation therapy. For those staged with T1-2, N1 tumors chemotherapy is advised for all. For those with T2, N2 disease, chemotherapy is the recommended treatment with the included option of radiation therapy plus chemotherapy. The overall consensus is that adjuvant chemotherapy is recommended for stages 1B to IIB. Defining optimal regimens which are efficacious yet minimally toxic is an ongoing task of research. We must continue to balance quality of life with quantity of life in our search for the optimal therapy.

- Lotfi Hadad, M.D., Medical Oncologist

2004 Prostate Cancer Awareness Campaign
"Home Run Series for Men's Health with Stan 'The Man' Musial"
Evansville Cancer Center kicked off its third annual prostate cancer awareness program "Home Run Series for Men's Health with Stan 'The Man' Musial" on Saturday, August 28th, 2004 at Evansville's Marriott.

The day's events opened with a luncheon for VIPs and sponsors followed with a presentation for the public. A panel of oncologists and urologists discussed the prostate and prostate cancer before a crowd of over 600 people. Mr. Musial took the stage and spoke of his legendary baseball career with the St. Louis Cardinals then addressed his own battle with prostate cancer urging men to be screened annually for this disease.

"Prostate Cancer: Speaking Man to Man" Television Program
On Monday, September 28th, 2004 from 8 to 9 p.m. Mike Blake of 14 WFIE hosted "Prostate Cancer: Speaking Man to Man," produced by the Evansville Cancer Center. This program featured urologists from the Tri-State area, oncologists from Evansville Cancer Center, and local prostate cancer survivors. In addition, viewers had the opportunity to call into WFIE's studios and have their questions answered live by a panel of physicians.

Free Prostate Cancer Screenings Offered to Area Industries
This is the second consecutive year that Evansville Cancer Center has coordinated several prostate cancer screenings at area industries. The screenings were provided free of charge compliments of an AstraZeneca grant and assistance by Lab-Corp, who processed the PSA blood tests. Several urologists generously donated their time to provide digital rectal exams as part of the prostate cancer screening.

As of November 2004, 306 men were screened for prostate cancer. Of that number, 18 men were found to have PSA's of 4 or higher and were instructed to schedule an appointment with their primary care physician or a urologist for further evaluation or testing. As with last year's results, a little over one-half of the men who participated in the screenings had never had a PSA blood test. All of the participants were given educational materials on prostate cancer.

Evansville Cancer Center would like to thank those who participated and assisted in any aspect of the 2004 prostate awareness campaign!

The Evansville Cancer Center would also like to thank the urologists in the Tri-State area, AstraZeneca, and LabCorp for teaming with us to provide educational awareness of prostate cancer and free prostate cancer screenings. William Fisher, MD, Phillip M. Gilson, MD, Barney Maynard, MD, Todd Renschler, M.D., Bruce Romick, MD, Bill Samm, MD & Michael Zenni, M.D. of Urological Associates, Inc. Thomas Gadient, M.D. of Urology Consultants & Paul F. Siami, MD of Welborn Clinic.
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