R. Sealy

Chemotherapy of small cell carcinoma of the lung with V.P. 16-213.

A Phase II Study of V.P. 16–213 administered to 47 patients suffering from small cell carcinoma of the bronchus. V.P. 16–213 was given as an intravenous infusion over 15 minutes daily for five consecutive days using 60 mg/m2/d at 14‐day intervals. Oral V.P. in 100 mg doses was given twice a week between the intravenous courses. Objective response rate for this drug compared favourably with that of other single agents reported. All but two patients showed a degree of response to treatment and 24 of 47 patients showed a true objective response to treatment. The overall median survival of these patients was 225 days and localized disease 278 days. The quality of survival was such that responders lived relatively normal lives up to the latter stages of their disease. The majority of patients had a marked response in performance status, 37 out of 47 showing an improvement. Three patients are alive and well at more than 27 months. In all cases the side effects were minimal. Alopecia was common and reversible haematological complications occurred. Severe toxicity was not encountered and the drug was well tolerated with supportive antiemetic therapy at onset of treatment.

Progress in the use of iodine therapy for tumours of the eye.

Developments in a new system of brachytherapy for tumours of the eye are reported. This involves the use of 125I sources with special screens and filters to avoid irradiation of vital structures and to produce a homogeneous radiation field. Methods for the treatment of tumours of the lids, conjunctiva, retina, choroid and lachrymal gland have been developed. Sixteen out of 20 treatments appear to have been successful. This system would seem to be a material advance on those previously reported.

Radiotherapy of regional epidermoid carcinoma of the lung: A study in fractionation

This paper reports a prospective randomized multicenter trial of two fractionation schemes in the supervoltage radiotherapy of locally inoperable epidermoid lung cancer. This study was stimulated by the need to provide improved and more acceptable treatment methods for patients with this condition, the most common cell type of lung cancer. The majority of such patients are not suitable for resection because of metastasis or because of extensive local disease, even though exploratory thoracotomy may be performed. It was therefore considered important to identify preferred methods of irradiation in this situation which is found in a large proportion of patients with lung cancer.

Treatment of head and neck cancer with intra-arterial cytotoxic drugs and radiotherapy

Advanced head and neck cancer thought to be incurable by irradiation or surgery alone or in combination was treated by intra‐arterial chemotherapy and radiation therapy. Two series have been treated, the one using methotrexate and alkylating agents, and the other Velban alone. The one‐year results of the second appear to be better. This line of investigation should be pursued further.

Irradiation with misonidazole and hyperbaric oxygen: final report on a randomized trial in advanced head and neck cancer

One hundred and thirty patients with locally advanced squamous carcinoma of the head and neck were treated in a prospective randomized trial to compare conventional irradiation (63.00 Gy in 30 fractions) with a combination sensitizer regimen of misonidazole and hyperbaric oxygen. The drug (2.0 gm/m2) was given with each of six fractions of 6.0 Gy in hyperbaric oxygen at 3 ATA. The results support a previous study and favor the combination at 1 year at better than the 10% level. This regimen could be useful for bulky primary or nodal disease.

The treatment of cancer of the uvula and soft palate with interstitial radioactive wire implants

A new method of implantation of the soft palate with radioactive wires is described. Experience with 25 patients is reported and the results analyzed. This method of treatment appears to be highly effective and avoids radiation complications.

The use of iodine-125 plaques in the treatment of retinoblastoma

125I has an energy of 27-35 keV which permits highly effective screening and makes it eminently suitable for treating ophthalmic tumours. It was first used for this in 1974 (Sealy et al., 1976), and since then a flexible system has been developed to treat a variety of such tumours including localized retinoblastoma. A gold foil backed plaque is custom built to cover the tumour(s). The turned edges reduce the dose and thus protect vital adjacent structures such as the optic nerve and lens. The iodine seeds are sealed in the plaque in a predetermined position to give the required dose. A range of doses and times have been used but the authors now aim to give a TDF of 100 to the apex of the tumour in two to three days. Ten tumours in the remaining eye of seven patients with bilateral retinoblastoma were treated. The size ranged from 3 X 3 X 2 to 10 X 10 X 6 mm. There were nine complete responses from 17-90 months and a partial response in one patient who died of metastases at ten months. Vision was maintained in all. Eight recurrent tumours in seven patients were also treated together with a subsequent new tumour in one of the patients. There were three complete responses at 28-39 months and six tumours persisted. Vision was maintained in three of seven patients. The only complication was a vitreous haemorrhage which was mild in two patients, moderate in one patient and severe in three previously treated patients. These latter three patients subsequently had the eye enucleated and were found to have recurrent tumour.

A report on misonidazole in a randomized trial in locally advanced head and neck cancer

A prospective randomized trial is reported involving 97 patients with locally advanced cancer of the head and neck. Using six large fractions of radiation (3600 rad in 17 days) the addition of misonidazole (2.0gm per m2 body surface) with each fraction did not increase the local control rate at one year. It is thought that this is probably because of an inadequate tumor concentration of the drug.

Hodgkin's disease. A clinicopathologic study of 122 cases

One‐hundred and twenty‐two cases of Hodgkins disease seen over a 15‐year period (1952–1967) have been reviewed. These patients have been followed for periods varying from 2 to 15 years. This study confirms the relatively good prognosis of the nodular sclerosing and lymphocytic predominant histologic types and of the patients first seen in an early clinical stage of the disease. A highly significant difference was noted between the survival of those patients who had at least a 2‐year remission following their initial therapy as compared to those who did not have such a remission. No significant difference was found in the survival curves of the colored as compared to the white patients in any of the histologic types.

The treatment of tumors by the induction of anemia and irradiation in hyperbaric oxygen

Because increased effects have been achieved when murine tumors are irradiated after a period of hypoxia and because of anecdotal clinical experiences of an improved result after irradiation of previously anemic patients in hyperbaric oxygen, the relationship between irradiation and increased survival was investigated in seventy‐two patients with advanced head and neck or cervical cancer. Anemia was achieved by means of a two‐stage isovolemic venesection maintained for seventy‐two hours, hemoglobin was returned to a normal level, and treatment in hyperbaric oxygen was started. Marked tumor shrinkage after the induction of anemia and before radiotherapy was seen and was probably disease, site, and hemoglobin level related. As a result, a possible new approach to cancer therapy is suggested. After completion of therapy, the 1‐year disease‐free survival for patients with head and neck and cervical cancer was not improved, but the 21‐month survival for cervical cancer was improved. Further studies are strongly urged.