Chemotherapy for bowel cancer

Chemotherapy is a name for medicines that damage cells which divide quickly. Cancer cells divide much faster than most normal cells, which is why these drugs work — they injure the cancer more than the healthy tissue around it. They also affect some normal fast-dividing tissues (the lining of the gut, hair follicles, bone marrow), which is where most of the side effects come from.

Unlike radiotherapy, which is aimed at one spot, chemotherapy circulates through the whole bloodstream. That is its strength and its limitation. The strength: it can reach cells that have travelled away from the original cancer and lodged somewhere we cannot see. The limitation: it affects normal tissues throughout the body too.

For bowel cancer, chemotherapy is given by your medical oncologist — the cancer specialist who looks after drug treatments. Surgery, radiotherapy and chemotherapy are usually coordinated together at a multidisciplinary team (MDT) meeting, where surgeon, oncologist, radiologist, pathologist and others agree on the plan.

Whether chemotherapy is recommended depends on the stage of the cancer at diagnosis and what was found at operation. The broad principles are:

• Stage I and most stage II colon cancer. Surgery alone is usually enough. Chemotherapy is generally not recommended because the risk of microscopic spread is low and the side effects of treatment would outweigh the small benefit.
• Stage II with high-risk features. A small group — those with tumour perforation, a blocked bowel at presentation, very few lymph nodes examined, or certain biological features — may be offered chemotherapy. The benefit is more modest than for stage III; the decision is individual.
• Stage III colon cancer (cancer in regional lymph nodes). Adjuvant chemotherapy after surgery is the standard recommendation. It reduces the chance of the cancer returning.
• Rectal cancer. Chemotherapy is often combined with radiotherapy before surgery, or given as a complete block of treatment before surgery in total neoadjuvant therapy (TNT). Adjuvant chemotherapy after rectal surgery is also used in some situations.
• Stage IV (metastatic) bowel cancer. Chemotherapy is a core treatment, often combined with biological therapies (drugs that target specific cancer features) or, for a small subgroup with mismatch-repair-deficient cancers, with immunotherapy. The goal shifts from cure to slowing the disease, easing symptoms, and lengthening good-quality life.

The MDT will look at the stage, the pathology of the tumour (including molecular features such as KRAS, NRAS, BRAF and mismatch-repair status), your overall health, and your goals — and recommend the regimen most likely to help.

The backbone of bowel-cancer chemotherapy is a drug called 5-fluorouracil (5-FU), or its tablet form, capecitabine. To this backbone, a drug called oxaliplatin is often added. The three main combinations used in Australia are:

A simpler regimen called capecitabine alone (no oxaliplatin) is used when oxaliplatin is felt to add too much risk — for instance in older patients, those with existing nerve problems, or where the expected benefit of oxaliplatin is small. Capecitabine alone is also commonly used during long-course radiotherapy for rectal cancer.

For metastatic disease, additional drugs and combinations are used — irinotecan (in FOLFIRI), bevacizumab (a biological therapy targeting blood-vessel growth), and the EGFR-targeted drugs cetuximab and panitumumab (only effective if the tumour is RAS and BRAF wild-type). Your oncologist will explain which apply to you.

The same drugs may be used in different settings, and the meaning of treatment is different in each:

• Adjuvant chemotherapy (after surgery). Given when the cancer has been removed but there is a meaningful risk that microscopic cells have spread to lymph nodes or beyond. The aim is to reduce the chance of recurrence. Stops at a fixed time.
• Neoadjuvant chemotherapy (before surgery). Given to shrink the cancer first or to treat microscopic spread early. Most commonly used in rectal cancer, often combined with radiotherapy or as part of TNT. Less common for colon cancer but its role is growing.
• Chemoradiotherapy. Capecitabine tablets taken alongside long-course radiotherapy for rectal cancer. The chemotherapy here is not at full systemic dose; it acts as a radiation sensitiser, making the radiotherapy more effective.
• Palliative chemotherapy. Given for stage IV disease that cannot be cured. The goal is to slow the cancer, ease symptoms, and lengthen good-quality life. May be continued, paused, switched between regimens, or stopped depending on response and tolerance.

Most people having intravenous chemotherapy for bowel cancer will have a port-a-cath (or PICC line) inserted before treatment starts. A port is a small device placed under the skin of the chest, with a fine tube running into a large vein. It avoids the need for repeated cannulas in the back of the hand and is left in place for the duration of treatment. Insertion is a short day-procedure done under local anaesthetic with sedation.

A typical FOLFOX or CAPOX treatment day:

1. Blood test a day or two before, or on the morning of treatment — to check that bone marrow, liver and kidney function are within the range needed for chemotherapy to be safe.
2. Pre-medications — anti-nausea drugs and steroids given before the chemotherapy starts. These help prevent sickness during and after the infusion.
3. The oxaliplatin infusion — given over 2 hours.
4. The folinic acid + 5-FU bolus (FOLFOX) — short infusions over another hour or so. For CAPOX, this is replaced by capecitabine tablets taken at home.
5. Take-home pump (FOLFOX only) — a small portable pump is connected to your port, which slowly delivers 5-FU over 46 hours. You go home with it attached, wear it under your clothes, and return 2 days later to have it disconnected by a nurse.
6. Days off — until the next cycle starts.

If you are taking capecitabine tablets, you take them at home twice a day, usually within 30 minutes of food, for 14 days followed by a 7-day rest. The dose is calculated from your body size and may be adjusted up or down based on side effects.

The side-effect profile depends on the regimen. Across the bowel-cancer drugs, the common short-term effects include:

• Fatigue. The most common and most pervasive symptom. Builds through the course of treatment. Light activity (walking, gentle exercise) helps more than rest alone.
• Nausea and reduced appetite. Modern anti-nausea medication keeps most people comfortable. Eat small, frequent meals and stay hydrated.
• Bowel changes. Diarrhoea is common with capecitabine and 5-FU; some people get constipation instead, especially with strong anti-nausea medication. Both are manageable, but tell your team early.
• Cold-induced numbness or tingling in fingers, toes, mouth and throat (oxaliplatin). Very characteristic — a strange "electric" sensation triggered by touching cold drinks or cold air. Use gloves in the freezer, avoid iced drinks for several days after each oxaliplatin dose, and warm your hands before going outside in winter.
• Hand-foot syndrome (capecitabine). Redness, dryness and tenderness of the palms and soles. Manageable with moisturisers and dose adjustment.
• Bone marrow suppression. A drop in white blood cells, red cells, and platelets. White-cell drops can increase infection risk — a high fever or chills during a cycle is a medical emergency, and you will be given a 24-hour number to call.
• Mouth ulcers. Especially with 5-FU. Salt-water rinses and dental hygiene help.
• Hair thinning — usually mild for FOLFOX, CAPOX and capecitabine. More noticeable hair loss is uncommon with these drugs (more so with irinotecan).

Most chemotherapy side effects settle within a few weeks of treatment finishing. A handful can persist or appear later — these are worth knowing about before treatment starts.

Longer-term effects worth knowing

• Oxaliplatin neuropathy. The cold-triggered tingling can shift over months to a persistent numbness or pins-and-needles in the fingers and toes that does not vary with temperature. It usually improves over a year or two, but can be lasting for some patients. Dose reductions or stopping oxaliplatin early are used if symptoms are progressing.
• Fertility. Chemotherapy can affect fertility. The risk depends on the drugs, dose, total duration, and your age. If you are of reproductive age and may want children in future, ask about fertility preservation (sperm storage for men; egg, embryo or ovarian tissue storage for women) before treatment starts. Pregnancy is to be avoided during and for a period after chemotherapy — reliable contraception is needed.
• Menopause and hormonal effects. Chemotherapy can bring on early menopause in women — sometimes permanent. Hot flushes, vaginal dryness and mood changes may follow. Speak to your team if these are affecting you.
• Heart and lung. 5-FU and capecitabine can cause chest pain or, rarely, heart-rhythm changes during an infusion — usually settling once the drug is stopped or the dose is reduced. If you have known heart disease, tell your team before starting.
• Cognitive changes ("chemo brain"). Some patients describe difficulty concentrating, finding words, or holding several things in their head at once during treatment and for some months afterwards. Most people improve over the first year off treatment.
• Second cancers. A small additional long-term risk of new cancers (particularly blood cancers) — uncommon, and small compared with the benefit of treating the current cancer.

Discuss any pre-existing health problems (heart disease, neuropathy from another cause, hearing loss, liver disease, swallowing problems) with your oncologist before starting. Modifications to the regimen are common and entirely standard practice.

For most patients, chemotherapy is one part of a wider plan that also involves surgery — and sometimes radiotherapy. The order depends on the cancer:

• Stage III colon cancer. Surgery first (typically a laparoscopic or robotic resection) followed by 3 to 6 months of adjuvant FOLFOX or CAPOX.
• Locally advanced rectal cancer. Increasingly, all the chemotherapy and radiotherapy is given before surgery — see total neoadjuvant therapy (TNT). For some patients with a complete response, surgery may even be deferred under a Watch and Wait pathway.
• Lower rectal cancer needing radiotherapy. Capecitabine tablets are taken during 5-6 weeks of long-course radiotherapy, then surgery (anterior resection or abdominoperineal resection) follows several weeks later.
• Stage IV bowel cancer. Chemotherapy is usually the first treatment, with surgery considered if the cancer responds well or if specific sites (such as liver metastases) can be resected with curative intent.

After chemotherapy and any other treatment finishes, regular bowel cancer follow-up surveillance is arranged. Long-term lifestyle, recovery from side effects, and emotional adjustment are part of the survivorship phase.