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PubMed1979

Complete remissions in metastatic breast cancer treated with combination drug therapy.

One hundred sixteen patients with metastatic breast cancer who achieved complete remission with combination chemotherapy were analyzed to ascertain the factors that affect the duration of complete remission and the patterns of relapse. The median duration of complete remission was 17 months. Disease recurred in 81 patients (70%) at periods ranging from 3 to 44 months after achievement of complete remission. The duration of complete remission was inversely related to the bulk of metastatic tumor. Twenty-three patients treated with combined oophorectomy and chemotherapy experienced the longest remissions (median duration of 33 months); only eight (35%) of them have relapsed. Seventy-six percent of the relapses occurred in previously known sites of tumor involvement; most of the remainder involved the brain. The short duration of complete remissions and tendency to relapse in sites of initial involvement suggest that patients with metastatic breast cancer who achieved complete remission with combination chemotherapy still had substantial residual tumor. Consolidation treatments, using hormonal therapy and non-cross-resistant chemotherapy along with irradiation to initial sites of metastases, whould be investigated to ascertain their usefulness in prolonging the remissions.

Adult↗
PubMedDate not supplied

Therapeutic studies in NZB/W mice. IV. Effect of combination drug therapy on immune complex deposition.

Azathioprine, cyclophosphamide, and methylprednisolone given individually to NZB/NZW mice retard the development of autoimmune nephritis and prolong survival in these mice. Administration of the combination of all three drugs is superior to one or two drug regimens. In the present study the kidneys of mice treated with all single, double, and triple drug regimens were compared for the degree of deposition of immunoglobulin and complement. The triple drug regimen significantly reduced overall deposition of immunoglobulin and complement compared with any other regimen. Complement and gamma2 were significantly reduced by triple drug therapy compared with any other regimen. The triple drug regimen reduced gamma1 compared with untreated and double drug treated mice. The single, double, and triple drug regimens significantly reduced gammaM deposition to about the same degree. Deposition of gammaA was not significantly reduced by any regimen. Circulating levels of these immunoglobulin classes were not reduced, a fact suggesting that the reduction in autoimmune nephritis resulting from triple drug therapy is associated with superior reduction in immune complex deposition rather than with generalized, non-specific immunodepression.

Animals↗
PubMed1979

Effects of combination drug therapy on the subcutaneous and pulmonary growth of a slow and a fast-growing C3H/He mammary carcinoma.

Changes in susceptibility to treatment with Cytoxan, methotrexate, 5-fluorouracil, and Adriamycin, single or in combination, have been studied during the initial and progressive stages of s.c. and pulmonary (via tail vein injection) growth of two transplanted syngeneic C3H/He mammary carcinomas. One tumor was fast growing, reaching a size of 3 mm from a 1-mm s.c. implant in 7 days; the second tumor would grow to the same size in 30 days. The tumor with the slower growth rate was more susceptible to drug treatment, manifested by delayed growth as well as by prevented growth. The slower-growing tumor also remained susceptible longer, when treatment was delayed, than did the faster-growing tumor. Pulmonary growth was more often prevented by drug treatment than was s.c. growth. Tumor implants s.c. which had reached palpable size could be reduced temporarily to impalpable size by effective drug treatment but were rarely cured. The importance of early treatment relative to the time of tumor implantation was indicated when early treatment with a single drug proved more effective than did delayed treatment with a more potent combination of drugs.

Animals↗
PubMed1978

A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy.

A prospective randomized trial was conducted comparing the clinical response of 78 previously untreated patients with advanced metastatic breast cancer to a combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or to a combination of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF). Sixty-two percent of the patients receiving CMF responded to treatment compared to an 82% response rate for the patients receiving CAF. Although within acceptable limits, hematologic and GI toxicity was greater with CAF. There was no significant difference in the duration of response to the two regimens. Therefore, the therapeutic difference between the two therapies is a higher initial response rate to the adriamycin containing regimen.

Breast Neoplasms↗
PubMed1976

Combination chemotherapy in the treatment of advanced breast cancer.

Seventy-two women with metastatic breast cancer were treated with multiple-agent chemotherapy. Fifty women were treated with 5 drugs in combination: 5-FU, methotrexate, vincristine, cytoxan, and prednisone; 22 were treated with the combination of 3 drugs: 5-fu, cytoxan, and prednisone. In 14 patients receiving 5 drugs and in 22 receiving 3 drugs, the multiple chemotherapy was the primary palliative treatment of extensive visceral metastases unsuitable for adrenalectomy. Results were similar with 6 responders in 14 (0.43) receiving 5 drugs, and 10 responders in 22 (0.45) receiving 3 drugs. The remaining 36 patients who were given 5-drug therapy all had previous adrenalectomy, and there were 16 responders (0.44). Toxicities from 3-drug treatment were substantially less severe than those from the 5-drug combination therapy. Whereas treatment-related death occurred in 6 of 50 patients receiving the 5-drug combination, no such incidence occurred in those receiving 3-drug combination therapy.

Adrenalectomy↗
PubMed1975

Seven-drug polychemotherapy in the treatment of advanced and recurrent squamous carcinoma of the female genital tract.

Single-agent chemotherapy of advanced and recurrent squamous carcinoma of the female genital tract has been largely ineffective. Combination-drug therapy which has augmented the efficacy of chemotherapy in numerous solid and nonsolid human tumors is usually attended by a degree of toxicity that has discouraged its use against malignancies exhibiting a poor response to single agents. A seven-drug regimen consisting of cyclophosphamide, 5-fluorouracil, actinomycin D, vincristine, cytosine arabinoside, methotrexate, and bleomycin administered during a 24 hour period at 4 week intervals was selected for clinical trial against squamous malignancies of the female genitalia because of its proved broad-spectrum activity among solid tumors and its low incidence of serious toxicity. Severe bone marrow depression occurred during only two of 98 drug cycles involving 23 patients. An objective tumor response was observed in nine of 18 evaluable patients. This regimen appears to be useful in the palliative management of squamous carcinoma of the female genital tract.

Adult↗
PubMed2026

Efficacy and safety of Ruxolitinib-based combination therapy in the patients with Myelofibrosis (MF): a systematic review and meta-analysis.

BACKGROUND: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm. Although Ruxolitinib, a JAK1/2 inhibitor, remains the cornerstone of MF treatment, it does not reverse disease progression, and resistance frequently emerges. These limitations have prompted investigation into combination therapies targeting pathways beyond the JAK-STAT axis. This meta-analysis aims to evaluate the efficacy and safety of Ruxolitinib-based combination therapies in patients with MF. METHODS: We conducted a systematic search of databases for studies published through August 1, 2025. Thirteen distinct Ruxolitinib-based combination regimens were included. Primary efficacy endpoints were ≥35% spleen volume reduction at 24 weeks (SVR35) and ≥50% reduction in total symptom score (TSS50). Safety endpoints focused on the incidence of grade 3/4 thrombocytopenia and anemia. Subgroup analyses were performed based on prior JAK inhibitor exposure and therapeutic mechanism of action. RESULTS: A total of 19 studies comprising 1,088 patients were included in the meta-analysis. Among JAK inhibitor-naïve patients, the combination of Ruxolitinib with Selinexor demonstrated the highest efficacy (SVR35: 92%; TSS50: 78%), followed by Ruxolitinib plus BMS-986158 (SVR35: 90%). For patients with prior JAK inhibitor exposure, Ruxolitinib plus Siremadlin (SVR35: 45%) showed notable activity. CONCLUSION: For JAK inhibitor-naïve patients, Ruxolitinib-based combination regimens demonstrated satisfactory clinical responses and the potential for meaningful disease control. For patients with prior JAK inhibitor exposure, the addition of combination therapy drugs may further enhance the efficacy. Personalized treatment selection remains essential, as therapeutic efficacy is significantly influenced by prior JAK inhibitor exposure.

Humans↗
PubMed1979

Seizures during lithium-amitriptyline therapy.

Epileptiform seizures occurred in a 34-year-old woman who was receiving amitriptyline and lithium carbonate therapy for treatment of endogenous depression. While receiving amitriptyline maintenance therapy, she was given lithium on two separate occasions, and despite serum levels of lithium in the therapeutic range, grand mal seizures developed. The seizures may represent a toxic reaction either to lithium or to combined drug therapy. Controlled studies are needed to evaluate both the efficacy and toxicity of combined drug therapy in affective disorders.

Adult↗
PubMed1979

Kinetics and metabolism of carbamazepine during combined antiepileptic drug therapy.

The kinetics of carbamazepine using 15N-carbamazepine were investigated in epileptic patients during combined anticonvulsant therapy. The 15N-carbamazepine plasma half-lives ranged from 5.0 to 13.6 hr with a mean of 8.2 hr. These half-lives are appreciably shorter than reported during chronic carbamazepine monotherapy. Predicted steady-state plasma levels and observed plasma levels of carbamazepine were in excellent agreement. Between 32% and 61% of the dose administered is excreted in the urine as carbamazepine-trans-diol, 5.2% to 8.8% as 9-hydroxymethyl-10-carbamoyl acridane, 1% to 1.4% as 10,-11-carbamazepine epoxide, and 0.5% as carbamazepine. The data indicate that it is the epoxide-diol pathway which is induced during long-term treatment. Concomitant therapy with primidone, phenytoin, phenobarbital, ethosuximide, or methsuximide further induces carbamazepine metabolism.

Adult↗