Common toxicity criteria

Systematic classification of the side effects of chemotherapy. From grade 3 on, we speak of serious side effects. The occurrence and extent of therapy-related side effects is the most important target variable for the assessment of oncological therapy concepts, along with the tumour remission rate, survival and quality of life. A distinction must be made between acute (< 90 days after the start of therapy) and chronic side effects (> 90 days after the start of therapy). The"Common Toxicity Criteria" (CTC) serve to record acute side effects and expand or modify the WHO system (see table). See also the cutaneous ADRs(drug exanthema).

The classification is based on 4 (5) degrees of severity:

• Grade 1: Low/light NW decays spontaneously and without specific therapeutic countermeasures; the intended oncological therapy can be continued without interruption.
• Grade 2: Moderate/clear side effects; they are usually treated on an outpatient basis and with simple medication (e.g. peripheral analgesics, steroids, oral antibiotics). Grade 2 NW do not cause any significant delay, dose modification (< 10 percent) or interruption of the intended oncological therapy.
• Grade 3: Severe or pronounced LV often requires hospitalization for the initiation of intensive drug and support measures (e.g. centrally acting analgesics, intravenous administration of antibiotics, percutaneous endoscopic gastrostomy [PEG]) and leads to interruption or significant delay (> 7 days) and/or dose modification.
• Grade 4: Life-threatening NW requiring immediate emergency hospitalisation, immediate intensive medical care or surgical intervention. They force the immediate, but possibly only temporary interruption of the intended oncological therapy, otherwise they can lead to the death of the patient within a short time.
• Grade 5: Organ-specific NW leading to death.

ADRs are further subdivided according to frequency into:

• very frequent >1:10
• frequent (> 1:100 <1:10)
• occasionally (>1:1,000<1:100)
• rare (>1:10,000 <1:1,000)
• very rare (<1:10,000 including individual reports).

Side effects can only be fully and correctly identified if all relevant systemic and organ-specific parameters are prospectively and regularly documented. Besides a careful anamnesis and subtle physical examination, laboratory controls and imaging procedures are necessary. In this way, any necessary adjustment of the oncological therapy (therapy delay or dose reduction) can be made in good time and, if serious side effects occur, supportive therapy can be initiated and carried out quickly and comprehensively.

There are general requirements for a standardised and systematic documentation of side effects: The classification must be internationally accepted and compatible, for example with regard to linguistic clarity and applicability in different health care systems. In principle, acute and chronic side effects must be distinguished.

Acute side effects occur during or within 90 days after oncological therapy.

Chronic side effects: Therapy related effects from day 91 onwards are evaluated as chronic side effects. Chronic side effects can, but do not necessarily develop from acute side effects; they often only become clinically manifest later and independently of the occurrence and extent of acute side effects, for example cardiotoxicity after anthracyclines or radiation effects on the spinal cord (Lhermitte's syndrome).

Practical implementation: For the practical recording of adverse drug reactions in oncological clinics and practices, a standardized documentation format should be used that lists the main and secondary criteria of the CTC classification. By ticking "yes/no" boxes or entering numbers for the severity levels, the individual secondary criteria should be precisely documented at all times.

1. Berdel WE et al (1994) Standard Operating Procedures (SOP) of the Phase I/II study group of the Association for Internal Oncology (AIO) in the German Cancer Society. Oncology 17: 311-338
2. Müller RP et al (1999) Common Toxicity Criteria (CTC): Documentation of side effects in oncology. Dtsch Ärztebl 96: A-489/B-433/C-397
3. Seegenschmiedt MH, Sauer R (1993): Systematics of acute and chronic radiation effects. Radiation therapy oncol 169: 83-95
4. World Health Organization (1979) WHO Handbook for reporting results of cancer treatment. World Health Organization Offset Publication No. 48, Geneva