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Biomedical subjects

G J Hill

Publications and source records attributed to G J Hill.

13 recordsLinked to original sources
PubMed1979

Dacarbazine and melphalan. Enhancement by dosage scheduling of the effect in combination treatment on the Harding-Passey melanoma in C3D2F1 mice.

The best combination and schedule for dacarbazine and melphalan with the Harding-Passey melanoma in C3D2F1 mice is achieved when dacarbazine is administered first, followed by melphalan, given on either the day of dacarbazine therapy or the first three days after dacarbazine is given. When dacarbazine is given first, followed by melphalan on day 0, 1, 2, or 3, the effect of the two drugs is considerably more than additive. Other schedules reduce the outcome to a simple additive effect, or to an outcome that is less than additive, in which the combination is less effective than melphalan used alone. The effect of variations in the order and schedule of drug administration should be investigated in future trials of cancer chemotherapeutic agents, since profound effects may occur with these variations.

Animals↗
PubMed1979

Combination chemotherapy for soft-tissue sarcomas: a phase III study.

A total of 144 patients with advanced sarcomas were entered into a randomized prospective protocol with four treatment arms utilizing different combinations of chemotherapeutic agents. Of these, 120 patients (83%) were judged acceptable. Treatment 1: actinomycin-D (Act-D), 0.01 mg/kg IV, days 1--5; phenylalanine mustard (L-PAM), 4 mg PO, days 1--10 every six weeks. Treatment 2: Act-D, 0.01 mg/kg IV, days 1--5; L-PAM, 4 mg PO, days 1--10; vincristine, 1 mg IV, days 1, 8, 15, 22, 29, 36, repeat every six weeks. Treatment 3: Act-D, 0.01 mg/kg IV, days 1--5; L-PAM, 4 mg PO, DAYS 1--10; NSC-1026, 200 mg/kg IV, days 1--6. Treatment 4: Adriamycin, 0.4 mg/kg IV, days 1, 2, 3, 8, 9, 10, then 2XWK starting day 15 (max. 1,200 mg). There was a provision that upon progression of the disease in the first three treatment regimens, patients would be crossed over to Treatment 4. Responses were as follows: 1 - Partial Response (PR) 1/25; No Change (NC) 9/25 (36%). gF2 - NC 17/26 (65%). 3 - NC 13/25 (52%). 4 - Complete Response (CR) 1/41; PR 6/41; (15%); NC 27/41 (66%). Clearly Treatment 4 was the best arm, with a 17% response rate and an initial progression rate of 17%. The only other response was a partial in 1. The difference is statistically significant (H = 17.247, P = 0.0006). If the responders to Adriamycin were analyzed without crossovers, the response rate would be 22% (6/27). (H = 14.079, P = 0.003). Median times to progression were 12.5, 8.7 weeks for 1 and 2, and 5 weeks for 3 and 4. There was no significant difference in the median survival times among the four treatment arms. It appears that Adriamycin as a single drug is superior to the drug combinations and would probably be even more effective used in combination with known active agents.

Antineoplastic Agents↗
PubMed1979

5-FU versus combination therapy with tubercidin, streptozotocin, and 5-FU in the treatment of pancreatic carcinomas: COG protocol 7230.

From May 1972 until May 1976, 105 patients were entered on Central Oncology Group protocol 7230 to compare the combination of streptozotocin, tubercidin, and 5-fluorouracil (5-FU) versus 5-FU alone in the treatment of adenocarcinoma and islet cell carcinoma of the pancreas. Twenty-nine were not evaluable. Thirty-six evaluable cases received 5-FU, and 40 received the combination, with no significant difference in time to progression or survival. Toxicity in the two regimens was somewhat different but was essentially similar in magnitude. Results indicate no benefit in the treatment of adenocarcinoma of the pancreas with the three-drug combination over 5-FU alone. All of the islet cell tumor patients benefited from the combination by response or arrest of progression of disease. Further study should be directed toward the use of this combination in the treatment of functioning and non-functioning islet cell tumors of the pancreas.

Adenocarcinoma↗
PubMed1979

Effects of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea, and L-phenylalanine mustard on B16, Cloudman S91, and Harding-Passey mouse melanomas.

The effects of 5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC), 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU), and L-phenylalanine mustard (L-PAM) have been compared by using three i.p. transplanted mouse melanomas: the B16 melanoma in C57BL/6 mice; the Harding-Passey (HP) malanoma in BALB/c X DBA/2F1 (hereafter called CD2F1) mice; and the Cloudman S91 melanoma in DBA/2 mice. HP melanoma responds well to all three drugs. S91 responds only to L-PAM and MeCCNU. DTIC may accelerate death in mice bearing this tumor. B16 responds well to L-PAM and moderately well to MeCCNU and to multiple injections of DTIC. The best response to DTIC and MeCCNU is given by HP, while the best response to L-PAM is given by S91. Tumor cell-doubling times were found to be 1.5 days for B16, 2 DAYS FOR HP, and 3 days for S91. HP would seem to be the most responsive malanmoma with respect to the 3 agents studied. This may be due to an interaction between the chemotherapeutic agents and the host immune response, since the HP tumor arose in a noninbred mouse and is thus nonsyngeneic with the CD2F1 host. All three tumors appear to be interesting biological models for studying drug combinations and combined therapeutic modalities against melanoma.

Animals↗
PubMed1978

Adjuvant chemotherapy in large-bowel cancer: demonstration of effectiveness of single agent chemotherapy in a prospectively controlled,, randomized trial.

In a prospectively randomized study, the effect of adjuvant chemotherapy with 5-FU on survival and recurrence rates was analyzed in 299 evaluable patients with colorectal carcinoma who either underwent a curative or a palliative resection. In the treatment group, chemotherapy consisted of the intravenous administration of 12 mg/kg daily of 5-FU for 4 consecutive days, then 6 mg/kg on alternate days, to the point of toxicity, or to a maximum of five doses, followed by 12mg/kg weekly for 1 year. Some degree of drug toxicity was seen in the majority of patients, was rarely severe, and there have been no drug-related deaths. Analysis of the survival curves and disease-free interval curves reveal definite evidence of drug benefit in two unfavorable subgroups, namely patients with Dukes C tumors and in patients whose tumor was located in the rectum. In the chemotherapy groups, patients who were treated to toxicity (WBC less than 4000 mm3), the disease-free interval was significantly longer than the nonleukopenic patients. We conclude that the addition of 5-FU to the surgical treatment of colorectal carcinoma provides a small, but significant benefit in patients with colorectal cancer in certain unfavorable subgroups, namely patients with Dukes C lesions and patients with rectal carcinoma.

Clinical Trials as Topic↗
PubMed1977

Adjuvant chemotherapy with 5-fluorouracil after surgical resection of colorectal carcinoma (COG protocol 7041). A preliminary report.

In a prospectively randomized study the effect of adjuvant chemotherapy with 5-FU on survival and recurrence was analyzed in 274 evaluable patients with colorectal carcinoma who either underwent a curative or a palliative resection. In the treatment group, chemotherapy consisted of the intravenous administration of 5-FU 12 mg/kg daily for four consecutive days, then 6 mg/kg/per day on alternate days to the point of toxicity or to a maximum of 5 doses, followed by 12 mg/kg/week for one year. Drug toxicity was rarely severe and consisted of nausea and vomiting, diarrhea, stomatitis, leukopenia, and thrombocytopenia in slightly more than half of all patients. There have been no drug-related deaths. Analysis of the survival curves and disease-free interval curves reveal some evidence of drug benefit in both the curative group of resections and the palliative group of resections. However, this benefit is not significant except in those treated to toxicity. The disease-free interval after curative resection is significantly longer in patients treated with 5-FU to the point of toxicity with a white blood count less than 4,000 cells/mm3. We conclude that a preliminary analysis of the Central Oncology Group data in this trial does not make a convincing case for the use of 5-FU as an adjuvant to the surgical treatment of colorectal carcinoma.

Adenocarcinoma↗
PubMed1977

Evaluation of ureteral obstruction by early intravenous pyelography.

Acute ureteral obstruction was studied in dogs by intravenous pyelography at two, four, six, nine, 12, 24, 48 and 168 hours after total occlusion of the ureter. Ureteral obstruction was correctly diagnosed in all instances, if intravenous pyelography was performed within nine hours from the time of obstruction and if a two hour sequence roentgenogram was obtained. A variably diagnostic rate of 36 to 75 per cent occurred when intravenous pyelography was delayed until 12 hours or later. In ureters with a positive diagnosis, 65 per cent were correctly identified on the 15 minute film, 98 per cent on the one hour film and 100 per cent on the two hour film. Intravenous pyelography should be performed immediately after the onset of renal insufficiency to obtain maximal information, as deterioration in renal function from total ureteral obstruction rapidly causes inadequate excretion and concentration of contrast material and prevents visualization of an obstructed collecting system.

Acute Disease↗
PubMed1976

Multimodal surgical adjuvant therapy for a broad spectrum of tumors in humans.?

Co-operative investigation of clinical therapy for cancer is used to test hypotheses developed in single institutions and in animal research laboratories. The present studies in a large co-operative organization, the Central Oncology Group, are being conducted in seven major solid tumors in adults; in these studies patients with a poor surgical prognosis are being treated with preoperative or postoperative chemotherapy, preoperative radiotion therapy of these modalities. Results of studies currently underway or recently completed in 1,278 patients are summarized. In most instances, the research has demonstrated little or no apparent improvement in the disease free interval or the survival time from adjuvant therapy, although only on of the studies has been completed and fully evaluated thus far. In carcinoma of the colon and rectum and melanoma, mild toxicity from drug therapy has been associated with statistically significant improvement in survival times. These studies have produced base line information on disease free intervals, time to progression and survival time in patients with cancer who are seen in the participating institutions. These observations are expected to useful in the planning of future adjuvant studies.

Adult↗
PubMed1976

DTIC (nsc-45388) and combination therapy for melanoma. I. Studies with DTIC, BCNU (NSC-409962), CCNU (NSC-79037), vincristine (NSC-67574), and hydroxyurea (NSC-32065).

A total of 270 patients with metastatic malignant melanoma were entered into a randomized chemotherapy study conducted by the Central Oncology Group (COG) over a period of 2 years (COG protocol No. 7130). The study utilized DTIC, CCNU, BCNU, vincristine, and hydroxyurea. The results of therapy with DTIC alone were compared with three combinations: (a) DTIC, CCNU, and vincristine; (b) DTIC, BCNU, and vincristine: and (c) DTIC, BCNU, and hydroxyurea. There were 243 evaluable patients out of 270. The response rate was 17.3% (42 of 243 patients) for evaluable patients and 15.5% (42 of 270 patients) for all patients entered in the study. The results showed no statistically significant difference in the response rates among the four treatment arms. However, several significant points were observed: (a) A 13% response rate was obtained using a combination of agents that included DTIC in patients who had previously shown no response to DTIC used as a single agent. (b) There was a significant difference in survival time when comparing responders to those with no change and to those with progression. (c) Toxicity was noted to be greater in responders than in nonresponders. (d) Two of the four treatment arms were considered most advantageous due to the ease of administration. These treatment arms were DTIC, BCNU, and vincristine and DTIC, CCNU, and vincristine administered in 5-day courses every 6 weeks. (e) The percentage of response and length of survival were significantly greater in patients without brain or liver metastasis. (f) In comparing men to women there was no statistically significant difference in response in rates or durations of response. (g) There was no statistically significant difference in survival when comparing site of primary lesion.

Adolescent↗