Commentary - A comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars and Intended Copy Biologics in treating chemotherapy associated febrile neutropenia.

Filgrastim, human white cell growth factor, Granulocyte colony-stimulating factor (G-CSF), is a core medicine in the WHO list of Essential Medicines. For this reason, recent reporting of statistically significant safety and efficacy differences between reference and Biosimilar brands of filgrastim by Rastogi and the Indian Pharmacopoeia Commission in Toxicology and Applied Pharmacology in 2020 is of great concern [Shruti Rastogi et al. Towards a comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars in treating chemotherapy associated febrile neutropenia: Trends from decades of data. Toxicology and Applied Pharmacology Volume 395, 15 May 2020, 114,976. https://doi.org/10.1016/j.taap.2020.114976]. This commentary shows that the alarming report is a result of incorrect statistical tests misapplied to inappropriate data sets compounded by a further problem relating to the strict regulatory definition of a Biosimilar Medicine as opposed that of an Intended Copy Biologic. In contrast, the body of evidence from more than seven and a half thousand participants in Confirmatory Clinical Studies and Post Approval Clinical Studies as well as the Periodic Safety Update Reports confirms that European approved filgrastim Biosimilars show no meaningful difference in quality, safety or efficacy compared to the reference brand.

Heterotopic bone formation: irradiation of high risk patients.

The Royal Marsden Hospital has adopted a policy for patient selection for the use of adjuvant radiotherapy to prevent heterotopic new bone formation (HTBF) limited to those at greater than 50% risk. The treatment protocol is 7 Gy post-operative megavoltage radiotherapy at mid-plane, in one fraction, given within 72 h of surgery. Since the introduction of this protocol in 1993, 26 joints have been treated in 25 patients. The majority of cases were young people with acetabular fractures resulting from road traffic accidents, often alcohol related. Follow-up studies in this group of patients has proved difficult, as many fail to attend for follow up, and others have moved out of the catchment area. Of the 14 cases for which follow-up data is available, 13 remain fully mobile. One has not mobilized since the time of treatment and continues to use crutches. There is one case of recurrent HTBF seen on X-ray after 8 months, but the joint was mobile. By 5 years, all cases have failed to attend for follow-up. The true long-term risks of this treatment policy may not be known for 30 years. The failure of patients to attend even short-term follow-up is a potential problem for clinical oncologists.

Cervical lymph node relapses of head-and-neck squamous cell carcinoma: is brachytherapy a therapeutic option?

PURPOSE: To report the results of interstitial brachytherapy (IBT) without salvage surgery for isolated cervical lymph node relapses. PATIENT AND METHODS: From 1970 to 1989, 84 patients were treated; 76 patients had relapsed in sites of previous external beam radiation. In 72 patients, IBT was sole salvage treatment (mean, 56.5 Gy). In 12 patients IBT (mean, 38 Gy) was combined with further external beam radiotherapy (mean, 41 Gy). RESULTS: Local control in the neck was 49% at 1 year, 31% at 2 years, and 0% at 5 years. Overall survival was 33% at 1 year, 13% at 2 years, and 1% at 5 years. Significant toxicity occurred in 35% (7% fatal). Multivariate analysis shows survival after salvage was better for patients who had achieved initial control for > or =18 months before relapse (0% vs. 13% at 3 years, p < 0.0002). Lymph node control was better for patients who received total salvage dose > or =60 Gy (0% vs. 56% at 3 years, p = 0.0004). CONCLUSION: Given its poor efficiency and its toxicity, IBT must be considered only when surgery is contraindicated and if lymph node relapse occurs after a minimal interval of 18 months.

Ear-lobe keloids: treatment by a protocol of surgical excision and immediate postoperative adjuvant radiotherapy.

There is no universally agreed policy for treating keloid scars of the ear lobe following piercing. We treated 35 patients (34 women) for high-risk ear-lobe keloids; the average age was 24 years (range: 16-44 years). All had failed to respond to prior treatment with massage and silicone, and corticosteroid injection. The keloids were excised extralesionally and the defects were closed with interrupted prolene sutures. The operative scar was covered with topical 2% lignocaine-0.25% chlorhexidine sterile lubricant gel under a transparent adhesive dressing. Adjuvant postoperative radiotherapy of 10 Gy, applied as 100 kV photons (4 mm high-voltage therapy (HVT) Al), was given within 24 h of surgery. All keloid scars were controlled at 4 weeks' follow-up. At 1 year, three out of 34 cases followed up had relapsed (probability of control: 91.2%). At 5 years, a further four out of the remaining 31 patients had relapsed (cumulative probability of control at 5 years: 79.4%). There were no cases of serious toxicity.

Amlodipine gynaecomastia.

We report only the second published confirmed case of gynaecomastia caused by amlodipine (a dihydropyridine calcium channel blocker). Gynaecomastia developed in a 70-year-old male within 3 months of starting amlodipine, and symptoms resolved within 3 weeks of drug withdrawal suggesting a strong relationship between amlodipine and gynaecomastia in this patient. Recent research has suggested possible interesting novel mechanisms for amlodipine gynaecomastia, which are discussed.

Salvage treatment for inoperable neck nodes in head and neck cancer using combined iridium-192 brachytherapy and surgical reconstruction.

The results of debulking surgery and re-irradiation with radioactive implants (brachytherapy) are reported for 39 patients with inoperable metastatic neck nodes from primary head and neck cancers. For 13 patients conventional salvage by partial debulking surgery and brachytherapy proved effective, with 68 per cent control at 1 year, but six patients suffered severe radiation fibrosis, necrosis and contractures. Some 26 patients were treated by combined tumour debulking, skin resurfacing and brachytherapy implant. Initial tumour control and freedom from serious toxicity was achieved in 24 patients. Local control was achieved in 63 per cent of patients at 1 year, with a serious morbidity rate of 12 per cent.