European Journal of Cancer (1965)最新文献

The results obtained in the treatment of 45 cases of soft tissue sarcomas are presented. All cases were reviewed and classified according to the modern criteria of malignancy. The treatment schedule comprised: (1) Preoperative irradiation: two sessions of 650 cGy in 48 hr—Target volume: whole limb segment; (2) Surgical excision 48 hr later with systematic intraoperative histologic verification, until healthy tissue margins are obtained; (3) Postoperative irradiation 3 weeks later delivering a cumulative total dose of 5000 cGy to the preoperative volume and 6000–7000 cGy to a reduced volume encompassing the surgical region with protection of vascular axes where possible; (4) Chemotherapy: Actinomycin D 0.3 mg/m² half an hour before the first 5 sessions of post-operative irradiation; (5) Bilateral lung irradiation: 4 sessions of 375 cGy in 7 days to the whole chest. The results were as follows: Local recurrence rate was 12% at 5 years. In 21 cases in whom surgical excision was deemed histologically adequate, no recurrences were seen at 2 years (minimum follow-up). Survival at 5 years was 76%. Deaths were due to metastatic spread, especially to the lungs. These results show an improvement as compared with historical series. New progress should be sought in combining a more aggressive type of chemotherapy for cases with high metastatic risk.

One C. parvum preparation and two BCG (Bacillus Calmette-Guérin) strains have been evaluated for their effects, when injected intratumorally, on established growths of a transplantable rat mammary carcinoma of spontaneous origin. It was found that whilst the anti-tumor effect of intratumoral injection varied from experiment to experiment certain conclusions could be drawn. Thus for maximal effect the injection should be given as early as possible and at a high dose; furthermore, multiple intratumoral injections appeared to offer no advantage over a single injection. It was also apparent that the anti-tumor effect following intratumoral injection of C. parvum or BCG was not improved when the tumor-bearing animals were presensitised to these immunostimulants. Intratumoral C. parvum was also used as an adjunct to surgery in the treatment of metastases; however, in this model it did not improve the effect of surgery alone. It is concluded that under certain defined circumstances intratumoral injection can bring about tumor regression. However, the conditions under which it is effective may render this form of treatment of limited application.

Forty-seven patients with stage IV malignant melanoma were treated with pulses of Vincristine and DTIC. Intercalated, monthly BCG was administered by multiple puncture gun. No patient exclusions were made. The response rate was 38%; all complete responders (8.5%) were metastatic to skin and nodes only. The median survival of the responder patient group was 6.7 months (1–21) and 2 months (< 1–47 +) for non-responders. No significant differences were found for response nor survival length between patients grouped according to sex, severity of haematological toxicity, intervals from initial diagnosis to appearance of metastases or to start of therapy. Patients with the higher Karnofsky scores survived longer. No side effects attributable to BCG were noted and no serious haematological toxicity was encountered. Despite a high response rate, survival was disappointing, and represented the presence of metastases in more than one organ system with only a minority (13%) of patients having metastases in ‘favourable’ (skin, node) sites. A full description of metastatic sites and other prognostic features is necessary for future treatment evaluation.

Thirteen patients with disseminated nonseminomatous germ cell carcinoma, failing to respond to extensive prior chemotherapy including cis-platinum, were treated with high dose chemotherapy. Cyclophosphamide (4.5g/m²) and epipodophyllotoxin (VP-16) (600 mg/m²) were given followed by autologous bone marrow transplantation. In some cases 1,3 bis (β-chloroethyl)-1-nitrosourea (BCNU), adriamycin or platinum were also administered. Of 10 patients evaluable for response 9 responded; 4 patients achieved a complete remission and 3 a partial remission. Median response duration was 15 weeks (range 4 to 20+ weeks). Four patients died from treatment-related infections; 2 of whom entered the program already with fever and 3 of whom died after hematopoietic recovery. Major toxicities were bacterial and fungal infections. In patients treated with cyclophosphamide and VP-16 only, no fever was seen in 3 out of 9 courses. Granulocyte transfusion was given in only 1 of 9 courses. Neutrophils recovered to greater than 1.5 × 10⁹/liter by day 18–35 (median 23) and platelets greater than 100 × 10⁹/liter by day 16 to 42+ (median 21). Further experience with high dose cyclophosphamide and VP-16 followed by autologous bone marrow transplantation is needed to evaluate its value in the management of patients with disseminated nonseminomatous germ cell tumor failing front line conventional chemotherapy.

During the period 1964–1977, regional perfusion and wide local excision were used in the treatment of 104 patients with a locally metastasized malignant melanoma of the limbs. One hundred patients were considered in a study of 3-year and 5-year survival, which was 52% ($\text{52}\text{100}$) and 38% ($\text{30}\text{78}$), respectively. The 3-year and 5-year survival rates in 18 patients treated by normothermic perfusion prior to 1969 were 22% ($\text{4}\text{18}$) and 17% ($\text{3}\text{18}$), respectively; in 82 patients treated by hyperthermic perfusion after 1969, the 3-year survival was 58.5% ($\text{48}\text{82}$) and the 5-year survival was 45% ($\text{27}\text{60}$). The difference between the normothermic and hyperthemic group is significant at the 3-year and 5-year level (P < 0.005 and P < 0.025, respectively). The 5-year survival in those treated by hyperthermic perfusion was 42% in stage II (n = 12) and 46% in stage III (n = 48), the difference not being significant. The male 5-year survival was 36% ($\text{8}\text{22}$), while the female was 53% ($\text{20}\text{38}$). The 5-year survival for tumours of the arm and those of the leg was 23% ($\text{3}\text{13}$) and 51% ($\text{24}\text{47}$), respectively. No significancy could be demonstrated between these groups. Of the entire group of 100 patients, 35 developed a local recurrence after perfusion; in 11 there was simultaneous general metastazation as well. The recurrence developed within 2 years after perfusion in 27 (77%) patients and 16 (76%) died within 2 years of recurrence.

The activities of 6-phosphogluconate dehydrogenase, phosphofructokinase and α-glycerolphosphate dehydrogenase were measured in primary carcinomas from a series of 333 patients with carcinoma of the breast and the usefulness of these estimations as additional prognostic parameters was evaluated. The patients in the series were followed for up to 50 months during which time 84 patients have developed recurrent disease. Life table analyses of the results showed that the probability of remaining free from recurrence was greater in women whose carcinomas had low activities of 6-phosphogluconate dehydrogenase and phosphofructokinase and high α-glycerolphosphate dehydrogenase activity. Low ratios of α-glycerolphosphate dehydrogenase to 6-phosphogluconate dehydrogenase were associated with a considerably increased risk of recurrence. These findings further indicate the usefulness of such assays as an aid to prognosis.

Coadministration of Tween 80 enhances the activity of adriamycin against selected experimental tumors in mice. Although some investigators have suggested a direct effect of Tween 80 on tumor cells, we wished to determine whether altered plasma concentrations of adriamycin occurred which might account for the apparent therapeutic synergism. Male CDF₁ mice were treated i.p. with 6.7 mg/kg of adriamycin alone or combined with 5000 mg/kg of Tween 80 in physiologic saline. Fluorometric determination of adriamycin equivalents in plasma revealed significantly higher adriamycin concentrations 1 and 2 hr post treatment in mice that had received Tween 80. In three separate experiments, a significant, reversible increase in packed cell volume occurred in the peripheral blood of mice treated i.p. with Tween 80. This increase was maximal at 1–2 hr post treatment. The magnitude of the apparent plasma volume reduction accounted quantitatively for the increase in drug concentration.

Two hundred and seventy eight patients with advanced breast cancer who had oestrogen receptor (ER) analyses performed on primary or recurrent tumours were studied. Oestrogen receptor (ER) positive (ER ≧ 5 fmole receptor/mg cytosol protein) tumours recurred significantly more commonly in bone and ER negative (ER < 5 fmole receptor/mg cytosol protein) tumours recurred significantly more often in liver and brain. Patients with ER positive tumours had a significantly better survival after relapse. ER analysis of either primary or recurrent tumour gives some indication of the natural history of breast cancer.