Anti-Angiogenic Therapy

A tumor cannot grow past a few millimeters without its own blood vessels. Anti-angiogenic drugs block the signal that builds them.

Anti-angiogenic therapy treats cancer by blocking VEGF, the growth factor that tumors release to make new blood vessels grow toward them. Two kinds of drug do this. Antibodies such as bevacizumab, given as a drip every two or three weeks, catch VEGF in the blood before it reaches its receptor, and tablets such as sunitinib, axitinib, cabozantinib and lenvatinib block the receptor from inside the cell. Adding bevacizumab to chemotherapy for bowel cancer that had spread raised median survival from 15.6 to 20.3 months in the trial that led to its approval (Hurwitz and colleagues, New England Journal of Medicine, 2004), and paired with the immunotherapy drug atezolizumab it became a first treatment for liver cancer that cannot be removed (Finn and colleagues, 2020). Kidney, cervical, ovarian, lung, thyroid and brain tumors are treated this way too. This page explains how the drugs work, which cancers they treat and with what results, who should not receive them, the side effects and how they are managed, how treatment is scheduled around surgery, and how patients from abroad arrange it at Biruni Hospital in Istanbul.

How the drugs work

The same idea in the eye

The drugs

Why tumors do not simply starve

Blocking VEGF rarely kills a tumor outright.

The early hope was that cutting off new vessels would starve cancers to death, and in mice it sometimes did. In patients, bevacizumab alone shrinks few tumors. Its benefit comes mostly alongside chemotherapy or immunotherapy, and the explanation took years to work out. By pruning the chaotic, leaky vessels a tumor builds, the drug leaves a smaller network that carries blood more evenly, so chemotherapy reaches more of the tumor and pressure inside it falls. Blocking VEGF also lifts a brake that VEGF places on the immune system, since the growth factor keeps immune cells out of the tumor and dampens their activity once inside, and this is the reason the pairing with immunotherapy works in liver and kidney cancer. Tumors adapt in the end. They switch to other growth factors, borrow existing vessels or grow along them, and resistance develops over months.

The tablets are different. They block several receptors at once, including some on the cancer cells themselves, and on their own they shrink kidney and thyroid cancers in a large share of patients.

Bowel cancer

The trial that led to approval

The median duration of survival was 20.3 months in the group given IFL plus bevacizumab, as compared with 15.6 months in the group given IFL plus placebo (Hurwitz and colleagues, 2004).

Liver cancer

In patients with unresectable hepatocellular carcinoma, atezolizumab combined with bevacizumab resulted in better overall and progression-free survival outcomes than sorafenib (Finn and colleagues, 2020).

Kidney cancer

The median progression-free survival was significantly longer in the sunitinib group (11 months) than in the interferon alfa group (5 months), and the objective response rate was 31 percent against 6 percent (Motzer and colleagues, 2007).

The combinations of an immunotherapy drug with a VEGF tablet shrink tumors in more than half of patients and are now the usual first choice.

Other cancers

Who should not receive it

Side effects

Grade 3 hypertension was more common during treatment with IFL plus bevacizumab than with IFL plus placebo, 11.0 percent against 2.3 percent, but was easily managed (Hurwitz and colleagues, 2004).

• High blood pressure, the commonest effect, controlled with ordinary blood pressure tablets in nearly every patient.
• Protein in the urine, checked with a dipstick before each dose.
• Nosebleeds and gum bleeding, mostly minor.
• With the tablets, sore and peeling skin on the palms and soles, diarrhea, tiredness, mouth sores, a hoarse voice and an underactive thyroid.

Schedule and surgery

Treatment for patients from abroad

One coordinator from the international patients office handles arrangements from the first message through discharge and answers the same WhatsApp number once you are back home. The office works in English, Arabic, French, Russian, Serbian, Romanian and Spanish and books interpreters for other languages, and it arranges the visa invitation letter, airport transfers, daily transport and accommodation near the hospital. Halal, vegetarian and diabetic meals, a prayer room on site, and a female physician on request wherever the rota allows.

Living with treatment

Work, travel and exercise continue for nearly everyone.

The home routine is simple. Measure blood pressure each morning and evening and write it down. Moisturize hands and feet twice a day on the tablets, wear soft shoes and treat thickened skin before it cracks. Tell every doctor and dentist about the treatment before any procedure, since a tooth extraction or a minor operation needs the same pause as major surgery. Pregnancy has to be avoided during treatment and for six months after bevacizumab.

Cost