NEW YORK (AP) -- Bank of America's $8.5 billion settlement with investors is the largest any bank has ever paid. It might help assuage worries about how deep the bank's mortgage problems might be and how long it might take to settle them. But for the nation's largest bank and its CEO Brian Moynihan, the slate is far from clean. The payout settles claims by just 22 investors who said Bank of America Corp. sold bonds based on substandard home mortgages. The bonds fell in value when the housing market collapsed and left the investors with losses on $424 billion worth of mortgages. The $8.5 billion settlement eclipses the last three years of earnings at the Charlotte, N.C. bank. The uncertainty about just how bad Bank of America's mortgage issues might be has scared investors and led to a 31 percent decline in Bank of America's stock price since January of last year when Moynihan took over. "This is a major step forward for our company," Moynihan said in a conference call with investors on Wednesday. Wall Street is cheering the move, sending the stock up 3 percent, to $11.14 Wednesday. It has been one of the worst performing stocks in the S&P 500 index in the past year. But that rally could be short-lived. Analysts say the $8.5 billion is about double the amount they'd expected. The bank continues to fight other investor groups that are demanding similar settlements. Lawsuits from the Federal Home Loan Bank of Boston, bond insurers MBIA and Syncora Holdings linger. And Bank of America is likely to be ordered to pay a hefty portion of the estimated $20 billion multi-bank settlement over the mishandling hundreds of thousands of home foreclosures. Paul Miller, a bank analyst at FBR Capital Markets, says he's concerned about the bank's ability to increase earnings at a pace that would make up for these higher costs. These worries are magnified by the fact that the economic recovery in the U.S. is slowing. That could reduce the number of loans the bank is able to make to consumers and businesses. Bank of America is in worse shape than other major banks like JPMorgan Chase & Co. and Wells Fargo & Co. because of its purchase of Countrywide for $4 billion in 2008. What seemed like a bargain price for the country's largest mortgage lender has cost the bank tens of billions more in mortgage losses, regulatory fines, repurchases of poorly-written loans and expensive litigation. At the same time, Bank of America itself had written a fair amount of bad mortgages. As it stands, the bank services one out of every five U.S. mortgages. So even though most of the major banks sold the same kind of securities and have bad mortgages on their books, analysts say they are in better shape than Bank of America, which has $2.2 trillion in assets. The other banks don't have the same pressure to put the mortgage woes behind them. In March, the Federal Reserve didn't allow Bank of America to increase its dividend, citing uncertainty about the depth of its mortgage problems. It was the only denial issued to any of the four largest U.S. banks. And it raised questions over whether the bank was strong enough to withstand another economic downturn. The combined effect of the losses and the uncertainty prompted a reversal in the bank's longtime strategy of fighting claims from investors, Moynihan admits. Since the beginning of the year, the bank has struck large settlements with multiple investors totaling $12.7 billion. Most of the settlements are with investors that had purchased mortgages or mortgage backed securities. They want banks to buy back mortgages that had misinformation about qualifications of borrowers who received them. During the housing boom, lenders such as Countrywide routinely gave mortgages to people without documenting their income or ability to pay. This was a key driver of the financial crisis. In January, the financial institution paid $2.6 billion to settle buyback claims on home loans sold to Fannie Mae and Freddie Mac. In April, the bank agreed to pay up to $1.6 billion to Assured Guaranty Ltd., an insurer that also pressed the bank to repurchase shoddy mortgages. Some industry analysts say the string of settlements could open the door for similar agreements between investors and other large banks that sold mortgages, including JPMorgan, Wells Fargo and Citigroup. "It's like the tobacco lawsuits -- if Phillip Morris loses, it affects everyone else," said Matt McCormick, a portfolio manager and banking analyst at Bahl & Gaynor Investment Counsel in Cincinnati, which manages about $4 billion in assets. He says banks face multiple issues, ""none of which are easy or inexpensive fixes." Even if other banks are pushed into settlements now, the amounts will likely be less eye-popping, because Bank of America has more exposure to bad mortgages. Bank of America's chief financial officer Bruce Thompson said in a conference call with analysts that by the end of the second quarter the bank would place $20 billion in reserves to cover costs related to future litigation and investor demands. As a result of Wednesday's settlement and other mortgage-related costs, Bank of America said it will take a $14 billion charge in the second quarter and will report a net loss of $8.6 billion to $9.1 billion in the second quarter of 2011. That's up to 93 cents per share. The bank reports second quarter results on July 19.

SILVER SPRING, Md. (AP) -- A panel of cancer experts has ruled for a second time that Avastin, the best-selling cancer drug in the world, should no longer be used in breast cancer patients, clearing the way for the government to remove its endorsement from the drug.

The unprecedented vote Wednesday by the Food and Drug Administration advisory panel comes less than a year after the same panel reached the same conclusion.

The six members of the FDA oncology drug panel voted unanimously that Avastin is ineffective, unsafe and should have its approval for breast cancer withdrawn.

"I think we all wanted Avastin to succeed but the reality is that these studies did not bear out that hope," said Natalie Compagni-Portis, the lone patient representative on the panel.

The vote is not binding and FDA Commissioner Margaret Hamburg will make the final decision sometime after July 28. The drug is approved for multiple cancers and will still be available for breast cancer, though insurers are expected to drop coverage if it loses FDA approval.

The FDA began steps to remove Avastin's breast cancer approval in December, but Roche took the rare step of appealing that decision and lobbied the agency and Congress for a second hearing.

The dramatic, contentious tone of the two-day hearing underscored the difficulty of removing an option for cancer patients, even when backed by scientific evidence.

Immediately after the final vote, patients in the audience erupted in shouts against the FDA and its experts.

"What do you want us to take!? We have nothing else!" shouted Christi Turnage, of Madison, Miss. Turnage said her cancer has been undetectable for more than two years since starting therapy with Avastin.

A spokesman for the Abigail Alliance, which advocates for access to experimental medicine, said the vote should be overruled.

"This was a kangaroo court," said Steven Walker, the group's co-founder. "There wasn't one dissenting thought up there, let alone one dissenting vote."

Assuming the FDA follows through on the withdrawal, drugmaker Roche could lose up to $1 billion in revenue for its best-selling product, which generates over $6 billion per year. Avastin is FDA-approved for various types of colon, lung, kidney and brain cancer, which are not part of the debate. Doctors will still be allowed to prescribe Avastin for breast cancer, though insurers may not pay for it. When administration fees are included, a year's treatment of Avastin can cost $100,000.

Roche's Genentech unit argued the drug should remain available while it conducts more research on which patients benefit most from the injectable drug. The drug is approved for breast cancer that has spread, or metastasized, to other parts of the body. Such cancer is generally considered incurable.

"The data tell us it is better for women diagnosed with metastatic breast cancer to have Avastin as an approved treatment option," said Hal Barron, Roche executive vice president.

Wednesday's vote came after two days of hearings that often resembled a courtroom trial, complete with testimony, cross-examination and a final jury verdict. In a public comment period Tuesday, Avastin patients and their families took the role of witnesses against the FDA.

"Make no mistake, this hearing is a death trial, not of Avastin but of these women who rely on Avastin to stay alive," said Terry Kalley, whose wife takes Avastin for breast cancer.

Kalley formed a group called Freedom of Access to Medicines to protest and lobby the FDA. He says the group does not receive funding from Roche.

Panelists said Avastin's ability to slow tumor growth -- measured through medical imaging scans -- has not translated into meaningful benefit for breast cancer patients.

"I think as treating clinicians we have to ask ourselves: What are we doing in terms of helping patients? Simply delaying a change in a CT scan for a month or two is not significant unless it's accompanied by other improvements in how the patients are doing or overall survival improvement," said panelist Dr. Wyndam Wilson of the National Cancer Institute.

The FDA granted Avastin accelerated approval in 2008 based on one study in which it slowed growth of breast cancer tumors for more than five months when combined with chemotherapy.

But that delay shrunk to less than three months in follow-up studies when the drug was paired with other types of chemotherapy. Across all studies, patients taking Avastin did not live any longer and suffered side effects like infection, high blood pressure and blood clots.

Most cancer experts say the drug should remain available for patients who are already responding well, even if its approval is withdrawn.

"I think the FDA is doing the right thing since the drug has some serious complications," said Dr. Stephanie Bernik of Lenox Hill Hospital in New York. "However, there are definitely patients who are benefiting from the drug and if the FDA completely withdraws approval those patients may find it hard to get access."

One potential option to keep the drug available would be for Roche to pay for it when patients have no other option. The company already provides the drug for free to patients who meet certain financial criteria or don't have health coverage.

Roche has suggested that Avastin works differently depending on which chemotherapy drug it is paired with. The drugmaker essentially asked the FDA for time to repeat its initial study that had the strongest results, theorizing that Avastin works best with the chemotherapy paclitaxel. Such a study would not be completed before 2016.

But the FDA rejected that argument, saying there is no evidence Avastin interacts differently with various chemotherapies, and that continuing approval cannot be justified based on one study completed six years ago.

"No trial has shown that patients treated with Avastin lived longer than those not treated with Avastin," said FDA's director for new drugs, Dr. John Jenkins. "All clinical trials show an increase in serious adverse events."

The Avastin review will have broad repercussions for patients and the pharmaceutical industry.

Since the early 1990s the FDA has granted accelerated approval to dozens of drugs based on promising early results, on the condition that their effectiveness is confirmed in later studies. That policy has been praised by patients with HIV, cancer and other deadly diseases where access to experimental treatments can mean life or death.

But the flipside of the program means removing drugs from the market if their initial promise isn't confirmed by later studies. And until last year the agency had never removed a drug from the market because of incomplete or unconvincing follow-up data.

With the removal of that leukemia drug from Pfizer, and now the proceedings over Avastin, analysts say the FDA is poised to crack down on drugs whose effectiveness hasn't been confirmed in later studies.