Rome, Italy (SportsNetwork.com) - Reigning champion Novak Djokovic, second- seeded Roger Federer and seven-time champ Rafael Nadal secured berths in the quarterfinals, while third-seeded Andy Murray withdrew from the Italian Open, a clay-court French Open tune-up.

The world No. 1 stalwart Djokovic started off slowly before rebounding to beat Brazilian qualifier Thomaz Bellucci 5-7, 6-2, 6-3 and extend his winning streak to 19 matches.

The three-time Rome titlist and two-time runner-up Djokovic beat the nine-time finalist Nadal (7-2) in last year's Rome finale.

The Australian Open and Wimbledon champion Djokovic already owns three Masters titles this season. His quarterfinal opponent will be 2014 U.S. Open runner-up Kei Nishikori.

The former world No. 1 Federer got past 15th-seeded South African Kevin Anderson 6-3, 7-5, while the fourth-seeded former top-ranked Nadal handled 16th-seeded American John Isner 6-4, 6-4 at Foro Italico.

Federer squandered a 5-2 double-break lead in the second set as Anderson staged a comeback, but the Swiss icon broke again in the 12th game before serving out the match.

"I had to adjust and react differently in today's match than yesterday's match," said Federer. "It was so different, because it's Kevin and his amazing serve. There's only so much you can do on the return games. The first thing was not to get frustrated, because I was not seeing where he was serving."

Federer is a three-time runner-up in Rome, including 2006 and 2013 versus his great rival Nadal.

Nadal, meanwhile, improved to 6-0 lifetime against Isner, who hadn't had his serve broken in nearly a month before Nadal got him twice on Thursday.

"When I had chances I (took advantage)," said Nadal. "My serve was perfect the whole match. I played with (few) mistakes."

Nadal and Djokovic have combined to win the last 10 titles at this Masters 1000 tournament.

The 33-year-old Federer will take on Czech big man Tomas Berdych, while Nadal will face Swiss slugger and 2008 Rome runner-up Stan Wawrinka in Friday's quarterfinals.

Meanwhile, Murray said he was fatigued after winning each of the last two clay-court events in Munich and Madrid.

"It's been a very long three weeks for me, the longest I've ever had on clay," said Murray, who had never even reached a clay-court final before his triumph in Munich.

Murray followed that with a surprising win in Madrid, beating Nadal in the final.

"The point is I did not expect to do what I have done in the past few weeks," Murray added. "My body has never done that before on clay. My body's always found the surface difficult. I also don't want to risk making it worse. In the past maybe I've done too much."

The French Open is just over a week away, as the year's second Grand Slam starts May 24 in Paris. Murray's best results at Roland Garros were semifinal appearances in 2011 and last year.

"I wanted to play in this tournament, it's a big event with a lot of points on offer," Murray continued. "The time of year is tough for everyone, it's just one of those things."

Belgian David Goffin earned a spot in the quarterfinals with the walkover against Murray, who's still 10-0 on clay this season.

Also on Day 4, a fifth-seeded Nishikori eased past Serb Viktor Troicki 6-4, 6-3; a sixth-seeded Berdych barely snuck past Italian crowd favorite Fabio Fognini 6-3, 3-6, 7-6 (7-2); seventh-seeded 2010 runner-up David Ferrer tackled fellow Spaniard Guillermo Garcia-Lopez 6-1, 6-3; and an eighth-seeded Wawrinka topped Austrian Dominic Thiem 7-6 (7-3), 6-4.

Ferrer and Goffin will clash in the round of eight.

The 2015 Rome titlist will claim $708,000.