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Opera Star Luciano Pavarotti Has Surgery for Pancreatic Cancer


NEW YORK - Tenor Luciano Pavarotti has had what was described as successful surgery for pancreatic cancer and will be undergoing additional treatment, presumably chemotherapy, over the coming months here.

NEW YORK, July 7 - Tenor Luciano Pavarotti has had what was described as successful surgery for pancreatic cancer and will be undergoing additional treatment, presumably chemotherapy, over the coming months here, according to a spokesperson.

The 70-year-old Italian opera star, who is in semi-retirement, was reported to be recovering well following removal of a malignant pancreatic mass. He canceled all remaining dates for the year, said the spokesperson.

"Just as Mr. Pavarotti was preparing to leave New York last week to recommence his performance schedule in the UK, doctors, concerned with results from a routine medical test, readmitted Mr. Pavarotti for assessment," said his manager, Terri Robson, in a statement posted on the singer's Web site.

"Mr. Pavarotti underwent a diagnostic evaluation and a malignant pancreatic mass was identified. Fortunately, the mass was able to be completely removed at surgery," Robson said.

The singer is recuperating in the New York hospital where the surgery was performed, which Robson did not identify. Whether he will be able to continue his worldwide farewell tour as planned in 2007 is uncertain, given the grim natural history of pancreatic cancer.

According to the National Cancer Institute, "cancer of the exocrine pancreas is rarely curable and has an overall survival rate of less than 4%. The highest cure rate occurs if the tumor is truly localized to the pancreas; however, this stage of the disease accounts for less than 20% of cases. For those patients with localized disease and small cancers (less than 2 cm) with no lymph node metastases and no extension beyond the capsule of the pancreas, complete surgical resection can yield actuarial five-year survival rates of 18% to 24%."

Carcinoma of the pancreas is currently the fourth leading cause of cancer deaths in the United States for both men and women, and will account for an estimated 32,300 death in 2006, according to American Cancer Society figures.

For reasons that are unclear, there has been a marked increase in the incidence of the disease over the past several decades. Risk factors include cigarette and cigar smoking; incidence rates for smokers are more than double that of non-smokers. Pavarotti has said that he smokes an occasional cigar, about 10 in three months during summers, and he has been seen in public lighting up a celebratory stogie on rare occasions.

Other apparent risk factors for pancreatic cancer include obesity (the singer famously struggled with his weight throughout his career), physical inactivity, chronic pancreatitis, diabetes, and cirrhosis. According to the ACS, pancreatic cancer rates are higher in countries where high-fat diets are typical. In a small fraction of cases, pancreatic cancer is hereditary.

Pancreatic cancer is rare before the age of 45, but the incidence rises sharply thereafter. The incidence is greater in males than females (male-to-female ratio 1.3:1), and in blacks (14.8 per 100,000 in black males compared to 8.8 per 100,000 in the general population).

Most patients diagnosed with pancreatic cancer have elevated levels of the cancer marker CA 19-9 at the time of diagnosis, but this marker has low specificity for cancer of the pancreas and is frequently elevated in patients with various benign pancreaticobiliary disorders. This marker may be useful for monitoring disease progression following definitive therapy, but normal values do not preclude disease recurrence, according to the NCI.

There is no consensus regarding the optimal management of patients after resection of a pancreatic cancer and patients are typically advised to participate in clinical trials evaluating new approaches to chemotherapy.

"Patients with any stage of pancreatic cancer can appropriately be considered candidates for clinical trials because of the poor response to chemotherapy, radiation therapy, and surgery as conventionally used," according to an NCI statement.

In December 2005, researchers at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., reported that high-dose chemotherapy followed by chemoradiation can turn a large inoperable pancreatic adenocarcinoma into a smaller resectable lesion.

In 12 of 24 patients in a phase II study, tumors shrank by at least a third, and nine patients whose disease was borderline or unresectable before treatment were able to undergo surgery, reported J. Marc Pipas, M.D., and colleagues in the Annals of Surgical Oncology.

The trial tested a high-dose Taxotere (docetaxel) and Gemzar (gemcitabine) combination followed by twice-weekly Gemzar and external beam radiotherapy for six weeks. After treatment, patients were considered for resection.

Taxotere was given at 65 mg/m2 intravenously over one hour and Gemzar at 4,000 mg/m2 intravenously over 30 minutes on days one, 15, and 29. On day 43, radiotherapy was begun at 50.4 Gy with Gemzar at 50 mg/m2 intravenously over 30 minutes twice weekly for 12 doses.

Of the 12 patients whose tumors shrank significantly, one tumor, which had previously been judged inoperable, disappeared completely.

The high-dose regimen was fairly well tolerated, the researchers reported. All but one patient completed the full round of therapy. Grade 3 and 4 toxicities were common but manageable, with no neutropenic fever.

Seventeen patients underwent resection after therapy, and 13 of these (76%) had negative surgical margins, including four patients whose tumors had previously been judged unresectable. None of the 17 patients who underwent surgery developed local recurrence of the disease.

At a median follow up of 22 months, 10 patients remained alive, and five remained disease free. Cause of death in the other 14 patients included progressive metastatic disease (9), postoperative complications (2), stroke (1), chronic obstructive pulmonary disease (1), and unknown (1).

"The overall response rate of 50% is remarkable for this disease and is especially encouraging when combined with the high rate of margin-negative pathologic results (76%) in the 17 patients who underwent resection," the researchers said.

For patients with advanced, metastatic disease, however, there are few options beyond palliation of symptoms. Among the more promising recent developments in the field has been a newly approved regimen combining Xeloda (capecitabine) and Gemzar.

At ECCO 13, the European Cancer Conference in Paris in November 2005, British researchers reported that the Xeloda-Gemzar regimen can significantly extend survival in some patients with advanced pancreatic cancer compared with Gemzar alone.

In a randomized study, patients with advanced pancreatic cancer treated with the combination had a median survival of 7.4 months, compared with six months for Gemzar alone, according to David Cunningham, M.D., of the Royal Marsden Hospital in Sutton and colleagues at other centers in England.

Patients taking Gemzar alone, the gold standard for advanced pancreatic cancer, had a 19% one-year survival rate, compared with 26% for patients on the Xeloda-Gemzar combination.

"The combination of gemcitabine and capecitabine confers a survival advantage over standard gemcitabine monotherapy and may be considered as a new standard of care in advanced pancreatic cancer," said co-author Ian Chau, M.D., also from the Royal Marsden.

"Patients will enjoy an improvement in survival with an acceptable level of side effects. This combination could form a new treatment platform to which novel molecular targeted therapy can be added."

The investigators found the Gemzar-Xeloda combination significantly improved overall survival over Gemzar alone (hazard ratio 0.80; 95% CI 0.65-0.98; P = 0.026). The median survival for Gemzar alone was six months, compared with 7.4 months for the combination. The one-year survival rates were 19% for Gemzar alone and 26% for Gemzar-Xeloda.

After the data were adjusted for the extent of disease and patient performance status, the survival advantage for the combination remained significant (HR 0.77; 95% CI 0.63-0.95; P = 0.014).

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