The trial in this blog was originally undertaken in the mid-1990s. The trial followed up the patients who received the treatment after the trial for 25 years. This paper follows up the participants from the original trial and is one of the longest follow up osteosarcoma trials currently known.
Osteosarcoma (OS) requires multiple forms of treatment. It often combines chemotherapy with surgical intervention. The chemotherapy can be targeted to the tumour before surgery (known as neoadjuvant chemotherapy), or it can be given post-surgery (known as adjuvant chemotherapy). The type and severity of the tumour helps decide which treatment to follow. The most common approach is having chemotherapy before surgery. This is because if the chemotherapy doesn’t help reduce the size of the tumour, the doctors can consider other chemotherapy drugs to use after the surgery. This helps to improve treatment response rate.
This trial looked at adults (aged 16 years and over) with OS with treatment tailored to the patient ages. The treatment in this trial was a combination of CDDP and ifosfamide.
What are CDDP and Ifosfamide?
Ifosfamide is a type of chemotherapy. Chemotherapy is a type of medication that kills cancer cells. It acts throughout the whole body so it can target both the primary cancer site and any areas that it has spread to. There are many types of chemotherapy drugs, but they all act in a similar way by targeting cells that are dividing quickly, which is a key feature of cancer cells.
CDDP is also known as cisplatin. It is also a type of chemotherapy treatment which has been specifically used to target OS. Previous studies which used ifosfamide and cisplatin treatments had a good outcome in patients and had a good 5-year follow up rate.
The original trial – 1994 to 1998
The original trial took place between 1994 and 1998. In this period there were 60 patient participants. The patients were over 16 years old, with OS confirmed in the limbs, body, head or neck. Patients were not included in the trial if the OS had spread from its original location (this is known as metastasised OS).
The patients were divided into two age groups. Their treatment was tailored to their ages.
What happened in the trial?
- Patients aged 16 to 25 years old were given a combination of treatment including ifosfamide and cisplatin before surgery. After surgery, patients were given further chemotherapy treatment. This treatment was decided by how much of the tumour they had managed to remove and treat previously. The course of each treatment was 21 days.
- Patients aged 25 and over were given 4 courses of chemotherapy treatment before surgery to remove the tumour. Chemotherapy treatment was the same as the younger group. This was also combined with another drug called doxorubicin. Further treatment was given after surgery
After reviewing this first round of treatment, doctors decided to change the treatment for the younger patients. From 1994 to 1998 they received a similar course of treatment to the older patients. Changing a course of treatment in a clinical trial is common. In this trial it was because two of the younger group had a reaction to their treatment which was considered above a clinically acceptable level. Because of this, the doctors adapted the rest of the treatment course for the rest of the group.
What were the results of this trial?
Results are described as disease-free survival (DFS) and overall survival (OSL).
- Disease-free survival refers to the amount of time after treatment ends that a person remains well without any symptoms or signs of cancer. It is one way of measuring how well a treatment has worked.
- Overall survival refers to the length of time after treatment starts for a condition (such as cancer) that patients are still alive. It doesn’t define whether the person has illness or not.5 of the 9 patients who responded to treatment survived for more than one year after treatment.
At 5 years after the trial ended, half of the original 60 patients remained well and without signs of cancer (DFS) for at least 5 years after this trial ended.
At 10 years after the trial ended the level of survival was similar to what it was at 5 years. This was for both DFS and OSL.
At 25 years after the trial ended, disease free survival and overall survival had lowered slightly (to 47.8% and 55.9%). This is to be expected in cancer trials with a long term follow up.
The level of medicines used in chemotherapy had no reports of cardiac toxicity in the 25 year follow up period. Cardiac toxicity is heart damage arising from chemotherapy and can be a negative side effect of receiving treatment.
3 out of the 33 long term survival patients developed a diagnosis of secondary cancer. This is when cancer either spreads to other parts of the body or a new cancer develops in a different area of the body.
What can we learn from this trial?
- The treatment protocol in this study produced reasonable outcomes for long term survival up to 25 years post-treatment.
- This result does reflect similar findings at 5 and 10 year follow up in similar studies. This means that the treatment can be considered for adult OS patients.
This trial showed a reasonable treatment plan for adults with OS. The treatments resulted in low cardiac toxicity, which can be a problem in OS treatments.
The main takeaway from this trial is the long term follow up. This can give insight into long term outcomes and survival rates beyond the initial period of cancer and treatment.
Glossary
A multicentre research trial is a clinical trial that involves more than one independent medical institutions in enrolling and following trial participants.
A prospective trial reports what happens as they happen in time (e.g. at treatment, after treatment).
A PhaseThe different stages of clinical trials that must be done to investigate a new drug. Phase 1 is the first stage while phase 4 is the final stage. 2 trial is when a drug or treatment is being researched as to how effective and safe it is in larger (up to 300 people) groups of patients.
Neoadjuvant chemotherapy: Neoadjuvant chemotherapy is chemotherapy that a person with cancer receives before their primary course of treatment. The aim is to shrink a cancerous tumor using drugs before moving onto other treatments, such as surgery.
Adjuvant chemotherapy: Adjuvant chemotherapy refers to chemotherapy that people receive after another cancer treatment, such as surgery.
Disease-free survival: The amount of time after treatment ends that a person remains well without any symptoms or signs of cancer. It is one way of measuring how well a treatment has worked.
Overall survival: The length of time after treatment starts for a condition (such as cancer) that patients are still alive.
References:
- Blay JY, Penel N, Toulmonde M, Valentin T, Chaigneau L, Rios M, Saada-Bouzid E, Firmin N, Bertucci F, Marec-Berard P, Ray-Coquard I, Lervat C, Rolland F, Thyss A, Conroy T, Brahmi M, Dufresne A, Merrouche Y, Brunat-Mentigny M, Biron P, Bompas E, Perol D; French Sarcoma Group. Long term survival in adult osteosarcoma patients treated with a two-drug regimen: Final results of the OSAD93 phase II study of the FSG-GETO. Eur J CancerA disease where cells divide and grow uncontrollably and can spread to other areas of the body.. 2024 Sep;208:114228. doi: 10.1016/j.ejca.2024.114228. Epub 2024 Jul 15. PMID: 39018632.
- Comprehensive Cancer Information – NCI [Internet]. NCI Dictionary of Cancer Terms; [cited 2024 Aug 28]. Available from: https://www.cancer.gov/publications/dictionaries/cancer-terms/search/overall%20survival/?searchMode=Begins
- Comprehensive Cancer Information – NCI [Internet]. NCI Dictionary of Cancer Terms; [cited 2024 Aug 28]. Available from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/disease-free-survival
- MPH ZS. Medical and health information | MedicalNewsToday [Internet]. Adjuvant vs. neoadjuvant chemotherapy: What to know; 2022 Mar 28 [cited 2024 Aug 28]. Available from: https://www.medicalnewstoday.com/articles/adjuvant-chemotherapy